Hypertension, But not "Prehypertension," Increases Stroke Risk -- and Should Combination Therapy Include a Calcium Antagonist?

March 16, 2004

In This Article

First Dual Therapy Medicine Approved for Treatment of Hypertension and High Cholesterol

In February, the US Food and Drug Administration (FDA) approved the first dual therapy for hypertension and high cholesterol. Caduet, developed by Pfizer, combines amlodipine besylate and atorvastatin calcium, for blood pressure and cholesterol lowering, respectively. It is indicated for patients in whom treatment with both amlodipine and atorvastatin is appropriate, ie,

Amlodipine:

  • hypertension

  • chronic stable angina

  • vasospastic (Prinzmetal or variant) angina

Atorvastatin:

  • primary hypercholesterolemia (heterozygous familial and nonfamilial)

  • mixed dyslipidemia

  • elevated serum triglyceride levels

  • primary dysbetalipoproteinemia

  • homozygous familial hypercholesterolemia

  • pediatric patients with heterozygous familial hypercholesterolemia after failure of diet therapy

Caduet will be available in multiple dosing combinations, including fixed doses of amlodipine 5 mg or 10 mg each combined with atorvastatin at doses of 10, 20, 40, and 80 mg. This allows physicians flexibility to titrate doses to get patients to their blood pressure and cholesterol goals. It is stressed that the dosage of Caduet should be individualized on the basis of both effectiveness and tolerance for each individual component drug.

FDA approval was apparently based on the results of a double-blind, placebo-controlled trial in 1600 patients with both hypertension and dyslipidemia. The patients who took combined treatment with amlodipine and atorvastatin had significant dose-related reductions in SBP, DBP, and LDL-cholesterol compared with those who received placebo. Pfizer says that in clinical trials Caduet has been well tolerated, and it has been administered safely with a wide variety of other antihypertensive medications, including thiazide diuretics, beta-blockers, and angiotensin-converting enzyme (ACE) inhibitors. The most common side effects associated with Caduet were fluid retention, headache, dizziness, abdominal pain, and weakness, which were all mild to moderate. Caduet carries the usual warnings for calcium channel blockers and HMG-CoA reductase inhibitors.

A date for marketing Caduet in the United States has not yet been announced. In Europe, a regulatory submission for the drug was made in December 2003.

Clinical trial results from patients with elevated lipids and hypertension who were treated with amlodipine 5 mg plus atorvastatin 10 mg administered once daily in the Atorvastatin and Amlodipine in Patients With Elevated Lipids and Hypertension (AVALON) trial were presented at the recent 20th Scientific Meeting of the International Society of Hypertension, held February 15-19 in São Paulo, Brazil.[6] In the randomized, double-blind study, 847 patients received either the combination treatment, amlodipine or atorvastatin plus placebo, or a double placebo for 8 weeks.

Significantly more patients treated with amlodipine plus atorvastatin achieved their National Cholesterol Education Program (NCEP) Adult treatment Panel (ATP) III LDL-cholesterol goals[7] and their JNC VI blood pressure goals[8] at the end of the 8-week treatment period compared with either atorvastatin or amlodipine alone or placebo (45.5%* vs 28.8% vs 8.3% vs 3.5%, respectively; *P < .001 vs atorvastatin or amlodipine). The adverse event rate was similar in all the active treatment groups. Joel M Neutel, MD (Orange County Heart Institute and Research Center, Orange, California), who presented the AVALON results, referred to the combination therapy as the start of a very exciting new trend of providing a way of attacking multiple cardiovascular risk factors in patients with the metabolic syndrome.

processing....