A post hoc analysis of data from the Study on Cognition and Prognosis in the Elderly (SCOPE) suggests that candesartan cilexitil (Generic Atacand, AstraZeneca), an angiotensin receptor blocker, significantly reduces major cardiovascular events in the elderly, the cardiovascular mortality rate, and the total mortality rate.

At the annual meeting of the European Society of Hypertension, the researchers said that their reanalysis reflected the original intent of the study—which was to compare candesartan and placebo; for ethical reasons, however, candesartan and other antihypertensive treatments were also compared.

Patients in the three-step trial first received 8 mg of candesartan or placebo. In the second step, they received 16 mg of candesartan or placebo. In the third step, another drug could be added, including open-label antihypertensive treatment.

The researchers compared outcomes among the 1,253 drug candesarta and 845 placebo patients who did not receive addon therapy. The final difference in blood pressure reduction was 4.7 mm Hg in the treatment group and 2.6 mm Hg in the placebo group. The relative risk of a major cardiovascular event was 0.68; of cardiovascular mortality, 0.71; and of total mortality, 0.73.

A drug that was shown in a landmark clinical trial five years ago to save the lives of patients with heart failure may have taken lives instead.

In 1999, researchers showed that a little-used, 40-year-old drug significantly reduced death and hospitalization for patients with congestive heart failure. Those results were so compelling that the trial was halted ahead of schedule. Now Canadian researchers are reporting that spironolactone (Mylan Labs) might have had a much different effect. (The brand-name drug, generic Aldactone®, is made by Pfizer.)

The publication of the 1999 study resulted in a greater than fourfold increase in prescriptions for the generic drug over an 18-month period. That surge in use was accompanied by a tripling of hospital admissions and of deaths resulting from dangerous elevations of potassium (hyperkalemia), a known side effect of spironolactone. Highly elevated potassium levels can cause severe muscle pain and can disrupt electrical conduction in the heart, causing sudden death.

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BiDil® is now approved for the treatment of heart failure in self-identified African-Americans. The approval was based partly on results from the African-American Heart Failure Trial (A-HeFT).

Patients receiving BiDil® experienced a 43% reduction in death and a 39% decrease in hospitalization for heart failure, compared with rates for placebo, and decreased symptoms of heart failure.

The product contains two older drugs, neither of which has been approved for heart failure—hydralazine (Apresoline®, Novartis) and drug isosorbide dinitrate (e.g., Sorbitrate®, AstraZeneca).

As an anti-hypertensive agent, hydral-azine relaxes the arteries, and decreases the work of the heart. The anti-anginal agent, isosorbide dinitrate, relaxes the veins and arteries. Isosorbide seems to work by releasing nitric oxide at the blood vessel wall, but its effect usually wears off after half a day. Hydralazine may prevent this loss of effect. How the two drugs work together is not yet clear.

Patients taking warfarin (Generic Coumadin, Bristol-Myers Squibb) often report that they feel tired, and this may make it more difficult for them to adhere to long-term treatment. However, it might not be the warfarin that is causing low energy, say researchers from the Canadian Institutes of Health.

In a substudy of a double-blind trial in 13 outpatient thromboembolism clinics, patients who had received a one-month trial of open-label warfarin therapy for venous thromboembolism caused by a transient risk factor were randomly assigned to receive warfarin or placebo for two months. They were observed for another nine months after they stopped taking the study drug.

Thirty-nine patients were randomly assigned to continue taking canadian warfarin for two months, and 48 were assigned to receive placebo. Patients used a seven-point Likert Scale to rate their fatigue.

Overall, the researchers found no association between warfarin and fatigue. By the end of the study, the patients’ overall ratings of fatigue were 0.1 unit lower. Their global ratings for change of intensity of fatigue at two months and 11 months also showed a significant reduction over time and no association between increased fatigue and warfarin use.

The Candesartan medication and Lisinopril Micro-albuminuria (CALM) study was one of the first to show that combining two drugs—an angiotensin-coverting enzyme (ACE)-inhibitor and an angio-tensin II receptor blocker—might be more effective than one drug in keeping blood pressure (BP) down in patients with diabetes. The CALM II study aimed to compare the long-term safety and efficacy of dual blockade with a single drug.

Patients received either lisinopril (e.g., Generic Zestril, AstraZeneca) 40 mg daily or candesartan cilexitil (Atacand drug, Astra-Zeneca) 16 mg daily and canadian lisinopril 20 mg daily. Fifteen of the 75 patients also needed a thiazide diuretic because of insufficient BP reduction.

Both treatments reduced systolic BP and stabilized the urinary albumin-to-creatinine ratio. Dual blockade was more effective for daytime BP and 24-hour and night systolic BP, but the trend was not significant.

Novartis Pharmaceuticals has announced that the FDA has approved valsartan (Diovan tablet), an angiotensin receptor blocker, to reduce cardiovascular deaths in high-risk patients (those with left ventricular failure or dysfunction) after a heart attack.

The FDA also expanded the drug’s labeling for heart failure. Valsartan drug, indicated for the first-line treatment of hypertension, can now be prescribed for a broader range of patients and is no longer limited to patients with an intolerance of angiotensin-converting enzyme (ACE) inhibitors.

Spironolactone (e.g., Aldactone generic, Pfizer), a diuretic and aldosterone antagonist, may nearly triple the risk of upper gastrointestinal (GI) events such as bleeding and ulcers, according to a study from Erasmus Medical Center in Rotterdam, The Netherlands. Researchers studied data from 306,645 patients, of whom 523 had definite gastric or duodenal ulcer or upper GI bleeding. Those patients were matched with 5,230 controls. Most patients used spironolactone for heart failure, but some used it for hypertension, and one used it for liver cirrhosis.

The current use of spironolactone was associated with a 2.7-fold increased risk of a GI event. Patients taking higher doses had a five-fold increased risk. The risk was most pronounced when spironolactone was combined with ulcerogenic drugs.