Drugs that lower low-density lipoprotein cholesterol (LDL-C) concentrations can prevent formation, slow progression and cause regression of atherosclerotic lesions. Lipid-regulating drugs must be taken indefinitely; when they are stopped, plasma lipoproteins return to pretreatment levels in 2-3 weeks.

The treatment of atrial fibrillation includes ventricular rate control, anticoagulation, conversion to normal sinus rhythm and maintenance of sinus rhythm. The choice of therapies that can achieve these goals is discussed in the text that follows. Some drugs are recommended here for indications that have not been approved by the FDA.

The FDA has approved prasugrel (Effient - Lilly/Daiichi Sankyo), an oral antiplatelet drug, for use with aspirin to reduce the rate of thrombotic cardiovascular events in patients with acute coronary syndromes (ACS) being managed with percutaneous coronary intervention (PCI). It will compete with clopidogrel (Plavix) for such use.

Atrial fibrillation increases the risk of stroke by a factor of 5. A randomized controlled trial (ACTIVE W) in 6706 patients with atrial fibrillation and one or more additional risk factors (≥75 years old; hypertension; previous stroke, transient ischemic attack or non- CNS embolus; left ventricular ejection fraction <45%; peripheral vascular disease; or 55-74 years old plus diabetes or coronary artery disease) found that a vitamin K antagonist such as warfarin (Coumadin, and others) was superior to clopidogrel (Plavix) plus aspirin in preventing vascular events, especially ischemic stroke.1

Now another study (ACTIVE A) from the same group of investigators has compared addition of clopidogrel to aspirin with aspirin alone in 7554 patients with atrial fibrillation and one or more additional risk factors for stroke. All of these patients were considered “unsuitable” for treatment with a vitamin K antagonist. Vascular events, primarily stroke, occurred significantly more often with aspirin alone. Major bleeding occurred significantly more often with aspirin plus clopidogrel.2

Oral anticoagulation with a vitamin K antagonist such as warfarin continues to be the treatment of choice for patients with atrial fibrillation and one or more additional risk factors for stroke.3-5 In patients who cannot or will not take a vitamin K antagonist, clopidogrel plus aspirin appears to be more effective in preventing stroke than aspirin alone.

1. ACTIVE Writing Group of the ACTIVE Investigators. Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE W): a randomised controlled trial. Lancet 2006; 367:1903.

2. ACTIVE Investigators. Effect of clopidogrel added to aspirin in patients with atrial fibrillation. N Engl J Med 2009; 360:2066.

3. Antiplatelet and anticoagulant drugs. Treat Guidel Med Lett 2008; 6:29.

4. DE Singer et al. Antithrombotic therapy in atrial fibrillation: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008; 133 (6 suppl): 546S.

5. AS Go. The ACTIVE pursuit of stroke prevention in patients with atrial fibrillation. N Engl J Med 2009; 360:2127.

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Effective treatment of hypertension can prevent organ damage and death. The choice of drugs for initial treatment continues to be controversial.

Arterial and venous thrombosis are major causes of morbidity and mortality. Arterial thrombi consist of platelet aggregates held together by small amounts of fibrin. Antiplatelet drugs are the drugs of choice for prevention and treatment of arterial thrombosis, but anticoagulants are also effective, and their effects can add to those of antiplatelet drugs. Venous thrombi are composed mainly of fibrin and trapped red blood cells, with relatively few platelets. Anticoagulants are the agents of choice for prevention and treatment of venous thromboembolism and for prevention of cardioembolic events in patients with atrial fibrillation.

Drugs that lower low-density lipoprotein cholesterol (LDL-C) concentrations can prevent formation, slow progression and cause regression of atherosclerotic lesions. They should not be used as a substitute for lifestyle changes; a combination of diet, exercise and lipid-lowering drugs is optimal for prevention of coronary disease. Lipid-regulating drugs must be taken indefinitely; when they are stopped, plasma lipoprotein levels return to pretreatment levels in 2-3 weeks.

Statins have been shown to reduce the risk of stroke in patients at high risk for cardiovascular disease (Treat Guidel Med Lett 2005; 3:15). A recent issue of The New England Journal of Medicine includes the results of a study sponsored by the manufacturer in which 80 mg of atorvastatin (Lipitor – Pfizer) or placebo was given to 4731 patients without coronary artery disease who had had a stroke or transient ischemic attack (TIA) within one to six months before study entry (The Stroke Prevention by Aggressive Reduction in Cholesterol Levels [SPARCL] Investigators. High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med 2006; 355:549). Patients were not required to have elevated cholesterol levels to enroll. The authors conclude that the study results support starting atorvastatin treatment soon after a stroke or TIA.

The primary study endpoint was a nonfatal or fatal stroke. During a median follow-up of 4.9 years, patients treated with atorvastatin had 265 strokes compared to 307 strokes with placebo. Patients treated with atorvastatin had 56 fewer ischemic strokes and 22 more hemorrhagic strokes. They also had 39 fewer coronary events. There were 216 deaths among patients treated with atorvastatin and 211 among those treated with placebo.

Whether patients with a recent ischemic stroke or TIA would be as well protected against a recurrence and against coronary events by a lower dose of atorvastatin or by another less potent statin remains to be determined. The risk of myopathy and rhabdomyolysis with statins is dose-related; atorvastatin is the second-most potent statin on the US market (rosuvastatin is the most potent), and 80 mg is its maximum dose. Statins have an antithrombotic effect, and an increase in hemorrhagic stroke in patients with cerebrovascular disease treated with statins has been reported previously (Heart Protection Collaborative Study, Lancet 2004; 363:757). It is doubtful whether patients with a recent hemorrhagic stroke should be treated with statins at all, let alone a maximum dose of atorvastatin.

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When the use of aspirin for primary prevention of cardiovascular diseases was last reviewed in The Medical Letter, only one placebo-controlled prospective trial was available: the (male) Physicians' Health Study. Last year, a second large, randomized, placebo-controlled study was reported as part of the Women's Health Study. Recently a sex-specific meta-analysis of 6 trials, including these two, was published.

Clopidogrel (Plavix - Sanofi-Aventis and Bristol-Myers Squibb), an oral thienopyridine that inhibits platelet aggregation, is now being advertised directly to the public on television. Clopidogrel is approved by the FDA for secondary prevention of myocardial infarction (MI), stroke and other vascular events and for use in patients with acute coronary syndrome (unstable angina or non-ST-elevation MI), including those undergoing angioplasty. It is used off-label for patients with ST-elevation acute MI

The FDA recently approved the use of atorvastatin (Lipitor) to reduce the risk of heart attack and stroke in patients without heart disease who have type 2 diabetes plus other risk factors, with or without hypercholesterolemia. The agency also approved the drug's use to reduce the risk of stroke in high-risk nondiabetic patients without heart disease, whether or not they have hypercholesterolemia. Similar indications were previously approved for simvastatin (Zocor).

Alteplase, a recombinant tissue plasminogen activator (TPA; Activase - Genentech), has been approved by the US Food and Drug Administration (FDA) for intravenous (IV) treatment of acute ischemic stroke. Several thrombolytic agents, including alteplase, were previously approved for use in acute myocardial infarction and acute massive pulmonary embolism (Medical Letter, 29:107, 1987; 32:15, 1990).

hydrochloride (Ticlid - Syntex), a platelet aggregation inhibitor that has been available in Europe for more than a decade, was recently approved by the U.S. Food and Drug Administration to decrease the risk of thrombotic stroke in men and women who have had premonitory signs of stroke or have had a completed thrombotic stroke. The manufacturer is promoting the drug for patients intolerant to aspirin or with conditions for which aspirin has not been approved (previous thrombotic stroke; transient ischemic attacks in women). The drug has also been used for prevention of myocardial infarction.

Taking aspirin to prevent recurrence or worsening of cardiovascular disease has become a common practice in recent years (Medical Letter, 28:31, 1986). Now, the US Food and Drug Administration is considering whether aspirin can also be advertised for prevention of a first myocardial infarction in previously healthy people.

Cerebral arterial spasm frequently causes ischemic neurological damage after subarachnoid hemorrhage from a ruptured intracranial aneurysm. Nimodipine (Nimotop - Miles), a 1,4-dihydropyridine calcium-entry blocker, was recently approved by the US Food and Drug Administration (FDA) for oral treatment of such patients; an intravenous preparation is available only for investigational use.