The anti-anginal agent ranolazine, in phase 3 clinical trials, reduced anginal frequency in patients experiencing 3 or more anginal attacks per week despite daily treatment with amlodipine 10 mg/d said Peter Stone, MD, lead investigator of the Evaluation of Ranolazine in Chronic Angina (ERICA) trial.
An exploratory analysis of PROactive (Prospective Pioglitazone Clinical Trial In Macrovascular Events Study) demonstrated a significant reduction in the risk of a second coronary event in patients with type 2 diabetes who took pioglitazone.
Oral anticoagulant therapy proved superior to the combination of clopidogrel and aspirin in preventing adverse vascular outcomes in patients with atrial fibrillation (AF). This outcome was observed in a large, multicenter trial at the 2005 AHA meeting in Dallas, comparing warfarin therapy with combination antiplatelet therapy in patients with AF.
The American Heart Association (AHA) Scientific Sessions comprise the world's largest conference for scientists and healthcare professionals focusing on cardiovascular disease.
Short-term treatment with the macrolide clarithromycin may cause significantly higher cardiovascular mortality in patients with stable coronary heart disease, according to a randomized, placebo-controlled multicenter study that took place in Denmark and was published in the British Medical Journal (BMJ).
Men who have used 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors to reduce their cholesterol levels may be at less risk of developing prostate cancer, according to a case-control study published in the American Journal of Epidemiology.
ACE inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) possess a similar and significant ability to reduce the development of new-onset type 2 diabetes among patients with hypertension, coronary artery disease, and heart failure, according to a meta-analysis study published in Diabetes Care.
Acetaminophen at doses of more than 500 mg/d and nonsteroidal anti-inflammatory drugs (NSAIDs) at doses of more than 400 mg/d increase the risk of incident hypertension in younger and older women, according to cohort studies published in Hypertension.
Ranolazine (Ranexa, CV Therapeutics) is a partial fatty acid oxidase inhibitor that increases the amount of ATP produced from glucose and increases the ability of the myocardium to retain functionality despite a reduced oxygen supply. Ranolazine is under FDA review for the treatment of chronic stable angina (CSA). Ranolazine was first reviewed in the August 2003 issue of Formulary. Since the initial review of ranolazine by FDA, additional data have emerged that merit an update in this journal. Clinical trials have demonstrated the efficacy of ranolazine as both monotherapy and combination therapy in patients with CSA. Recently published clinical trials (MARISA and CARISA) have shown an improvement in symptom-limited exercise duration. The results of the ERICA trial demonstrated a reduction in weekly anginal attacks when ranolazine was added to maximum-dose amlodipine therapy. Headache and generalized weakness were the most commonly reported adverse events in clinical trials. Prolongation of the QT interval has raised concerns; however, a lack of development of ventricular tachyarrhythmias-specifically Torsade de Pointes-remains an important safety finding. (Formulary. 2005;40:323–328.)
Early use of clopidogrel, started prior to rather than at the time of angioplasty, reduces the risk of death, MI, or stroke by nearly half, reported Marc S. Sabatine, MD, MPH, lead investigator of PCI-CLARITY (Clopidogrel as Adjunctive Reperfusion Therapy).
The factor Xa inhibitor fondaparinux prevents death, MI, and refractory ischemia at 9 days as well as the low-molecular-weight heparin enoxaparin in patients with acute coronary syndromes (ACS), while reducing the incidence of bleeding.
Following the voluntary withdrawal of rofecoxib in September 2004 and the subsequent FDA-requested withdrawal of valdecoxib in April 2005, formulary decision-makers are considering options in navigating the changing pain management landscape. With one remaining COX-2 inhibitor available on the market (celecoxib [Celebrex, Pfizer]) and more cardiovascular (CV) risk data available for the class, the efficacy, adverse events, risk/benefit profiles, and costs of both COX-2-selective and nonselective NSAIDs are receiving more attention than ever.
Analyses of 3 retrospective databases found that warfarin is much less effective at preventing strokes in the real world in patients with chronic atrial fibrillation (AF) than it is in clinical trials. The retrospective data were reported at the ASA's International Stroke Conference 2005.
Clopidogrel reduces 28-day mortality in the treatment of patients with acute myocardial infarction (MI) when given on top of standard therapies, but metoprolol has no effect on in-hospital mortality when given during the acute phase of MI.
The American Heart Association (AHA) Scientific Sessions comprise the largest meeting of its kind held in the cardiovascular field, with several thousand presentations given each year. The recently concluded 2004 AHA Scientific Sessions, which took place in New Orleans, included presentations of trials that evaluated potential therapeutic compounds, as well as widely used and accepted compounds in new dosages or combinations, for the treatment of cardiovascular disorders. The compilation of clinical news that follows focuses on the cardiovascular pharmacotherapy trials of greatest interest to formulary decision-makers, including: CREATE, PEACE, A-HeFT, PROTECT, CLEAR Platelets, DIPOM, GEMINI, SHIELD, and RIO-NA.
A review of select agents in late-stage development for the treatment of arrhythmia, congestive/chronic heart failure, and pulmonary hypertension (PDF) (January 2005)
Researchers conducted a study to determine if self-reported sleep deprivation is associated with an increased risk of coronary events.
Valdecoxib meta-analysis finds increased cardiovascular risk
Nebivolol is a beta-blocker under FDA review for the treatment of hypertension. Nebivolol has unique pharmacologic properties, including high specificity for the beta-1 receptor and a nitric oxide-mediated vasodilatory effect. The agent provides significant blood pressure reduction from baseline values and as compared to placebo. Clinical trials have demonstrated that nebivolol reduces blood pressure similarly to atenolol, bisoprolol, amlodipine, nifedipine, lisinopril, and hydrochlorothiazide. The tolerability of nebivolol is similar to or better than that of these agents. If approved, nebivolol would likely be a viable alternative therapy for hypertension; however, additional studies are needed in patients with heart failure and coronary artery disease.
Rofecoxib voluntarily withdrawn from market due to cardiovascular risk
Initiating high-dose simvastatin (Zocor, Merck) early after an acute coronary syndrome (ACS) event does not result in significantly superior clinical outcomes compared to delayed initiation of low-dose simvastatin.This major finding of phase Z of the A to Z Trial is in contrast to the results of 2 previous clinical trials in which aggressive therapy with atorvastatin (Lipitor, Pfizer) was found to be superior to less aggressive statin therapy in reducing the risk of adverse clinical events in ACS patients.
The Warfarin/Aspirin Study in Heart Failure provided no evidence that aspirin is effective or safe in heart failure patients.
A study presented on August 25 at the 20th International Conference on Pharmacoepidemiology & Therapeutic Risk Management in Bordeaux, France, revealed that higher-dose rofecoxib (>25 mg/d) was associated with a greater risk of acute myocardial infarction (AMI) and sudden cardiac death (SCD) compared to other NSAIDs. The risk of AMI and SCD was also increased with lower-dose rofecoxib (25 mg/d) when compared with celecoxib. The maximum recommended daily doses of rofecoxib in the management of pain associated with osteoarthritis, rheumatoid arthritis, primary dysmenorrhea, and migraine attacks with or without aura are 25, 25, 50, and 50 mg/d, respectively.
A study presented on August 25 at the 20th International Conference on Pharmacoepidemiology & Therapeutic Risk Management in Bordeaux, France, revealed that higher-dose rofecoxib (>25 mg/d) was associated with a greater risk of acute myocardial infarction (AMI) and sudden cardiac death (SCD) compared to other NSAIDs. The risk of AMI and SCD was also increased with lower-dose rofecoxib (25 mg/d) when compared with celecoxib. The maximum recommended daily doses of rofecoxib in the management of pain associated with osteoarthritis, rheumatoid arthritis, primary dysmenorrhea, and migraine attacks with or without aura are 25, 25, 50, and 50 mg/d, respectively.
Current treatment options for acute coronary syndromes as well as chronic stable angina often include the use of percutaneous coronary intervention (PCI) with routine stenting. The clear benefits of stents have lead to their routine use for prevention of restenosis. However, the benefits of stenting demonstrated on some aspects of restenosis are compromised by the induction of restenosis by neointimal hyperplasia that is stimulated by standard bare metal stents. FDA has approved 2 drug-eluting stents (DES). DES create a local delivery system at the vascular site to reduce restenosis by neointimal hyperplasia. Multiple clinical trials have demonstrated the safety and efficacy of the use of DES. This article reviews the use of PCI in coronary artery disease, the evolution and pathophysiology of restenosis, and multiple aspects of DES technology. While DES may not be a direct pharmacy and therapeutics committee responsibility, committee members are being called upon to provide insights into pathway processes for medical technology review committees evaluating DES since these products contain a key pharmacologic component. There are also important adjunctive antiplatelet therapy protocols that need to be developed and adhered to in conjunction with DES in order to ensure optimal outcomes.
