Implantable Cardioverter Defibrillator DEBUTs as a Life-Saver in Thailand
Implantable cardioverter defibrillators (ICDs) provided full protection against sudden unexpected death associated with ventricular fibrillation in young Thai men in a study that appears in this week’s issue of the journal Circulation (Circulation. 2003;107:2221–2226). Sudden unexpected death syndrome (SUDS) is the most common cause of death among young men in Thailand.
In the DEBUT (DEfibrillators versus β-Blockers for Unexplained death in Thailand) trial, a total of 86 patients who were considered SUDS survivors or suspected SUDS survivors were randomized to receive either an ICD or propanolol. (Twenty of the subjects were in a pilot trial, and 66 were in the main study.) The primary end point was death from all causes. Secondary end points were (1) recurrent ventricular tachycardia or ventricular fibrillation or (2) cardiac arrest.
During a 3-year follow-up in the main study, there were 4 deaths in the β-blocker group and none in the ICD group, according to researchers from the Pacific Rim Electrophysiology Institute in Los Angeles, Calif; the Royal Thai Air Force Medical Center in Bangkok; Johns Hopkins University School of Medicine in Baltimore, Md; Maida University and Chulalongkorn University in Thailand; and the Statistical Consultation and Research Center of the University of Southern California School of Medicine in San Diego. Seven subjects in the ICD arm had recurrent ventricular fibrillation that was successfully treated by the defibrillator. The Data Safety Monitoring Board stopped the main trial early because of the preferred results in the ICD trial. In the combined pilot and main trials, there were 7 deaths in the β-blocker group and none in the ICD group. Twelve ICD patients received discharges because of recurrent ventricular fibrillation.
The researchers concluded that the ICD was a superior treatment to β-blockers in this population.
Cholesterol Control Eludes US Population
The mean serum total cholesterol concentration of the adult US population in the years 1999 and 2000 had changed little from that measured from 1988 through 1994, reported researchers from the latest National Health and Nutrition Examination Survey in a report in this week’s issue of the journal Circulation (Circulation. 2003;107:2185–2189).
The age-adjusted mean cholesterol concentration was 5.27 mmol/L (203 mg/dL) among all adults, reported the researchers, led by Earl S. Ford, MD, MPH, from the Division of Adult and Community Health of the National Center for Chronic Disease Prevention and Health Promotion of the US Centers for Disease Control and Prevention in Atlanta, Ga. The average for men was 5.25 mmol/L (203 mg/dL), and the average for women was 4.28 mmol/L (204 mg/dL). The researchers said the concentrations were little changed from a similar study conducted between 1988 and 1994. They noted, “The low percentage of adults with controlled blood cholesterol concentrations suggests the need for a renewed commitment to the prevention, treatment, and control of hypercholesterolemia.”
The premature closing, for what the sponsor called “commercial reasons,” of the CONVINCE (Controlled ONset Verapamil INvestigation of Cardiovascular End Points) trial, which had been designed to compare controlled-onset extended-release (COER) verapamil with the β-blocker atenolol and the diuretic hydrochlorothiazide, drew criticism from the editors of The Journal of American Medical Association (in which the 3-year results of the study were published) in the April 23/30, 2003, issue of the journal.
In an editorial (JAMA. 2003;289:2128–2131) that accompanied the report (JAMA. 2003;289:2073–2082), Bruce M. Psaty, MD, PhD, of the University of Washington in Seattle, and Drummond Rennie, MD, Deputy Editor of The Journal of American Medical Association, questioned the decision of the trial’s sponsors to end it 2 years early.
They wrote, “The recruitment and involvement of human research participants places clinical trials in a category decidedly distinct form the customary swapping and trading of traditional goods and services. When patients and other research participants are recruited for scientific investigations, they agree willingly to expose themselves to risk. Individuals often participate out of a sense of altruism, and counted among the most important reasons for joining trials are the improvements in their own health, the contributions to science, and the improvement of the health of others.”
“If CONVINCE had been continued to the originally planned completion, the improved blood pressure control associated with trial participants might well have produced substantial health benefits. The participants in CONVINCE were not only deprived of personal benefit from the completed trial, but also the social benefit of genuine scientific contributions from an adequately powered study. If the conduct of a seriously underpowered study is unethical, the willful creation of an underpowered study by the early stopping of CONVINCE seems unethical as well. What the company apparently treated as simple commercial matter rendered the original promise to participate in research that contributes substantively to medical knowledge impotent, useless, or fraudulent.”
“Medical research, even if it is conducted by the pharmaceutical industry, is not solely a commercial enterprise designed to maximize personal gain or company profits. The responsible conduct of medical research involves a social duty and a moral responsibility that transcends quarterly business plans or the changing of chief executive officers,” they write. “The findings of CONVINCE have been hobbled by the early stopping of this trial. Not only is power inadequate, but the investigators were placed in the difficult position of closing out the trial safely and on short notice.”
They add that in its current form, CONVINCE adds little new information to the other recent comparative trials. They conclude: “In light of ALLHAT [Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial], switching appropriate patients to low-dose diuretic therapy would at once improve health outcomes for patients and, one prescription change at a time, whisper an evidence-based reminder to the pharmaceutical industry about the social value and the public health importance of large long-term trials that are successfully brought to completion.”
The trial was supported by grants and contracts with G.D. Searle & Co, of Skokie, Ill, and Pharmacia, of Peapack, NJ.
The incomplete results of the trial indicate that the calcium channel blocker verapamil was not superior to the diuretic or β-blocker in reducing cardiovascular events in patients with hypertension. The study, conducted by Henry R. Black, MD, of Rush-Presbyterian–St Luke’s Medical Center in Chicago and colleagues at 661 centers in 15 countries, involved 16 602 patients diagnosed with high blood pressure and at least 1 more risk factor for cardiovascular disease. In the trial, 8179 subjects received 180 mg of verapamil, and 8297 received either 50 mg of atenolol or 12.5 mg of hydrochlorothiazide.
The authors wrote, “Systolic and diastolic blood pressure were reduced by 13.6 mm Hg and 7.8 mm Hg for participants assigned to the COER verapamil group and by 13.5 and 7.1 mm Hg for participants assigned to the atenolol or hydrochlorothiazide group. There were 364 primary cardiovascular disease–related events that occurred in the COER verapamil group versus 365 in atenolol or hydrochlorothiazide group. The treatment regimens showed some minor and statistically nonsignificant differences in the incidence of each component of the primary end point.”
The researchers found that although verapamil reduced the incidence of acute heart attack by about 18%, subjects in that group had a 15% increased incidence of stroke.
The authors wrote: “In summary, CONVINCE was unable to demonstrate equivalence of a COER verapamil–based antihypertensive regimen and a regimen beginning with a diuretic or β-blocker.” Considering this along with other studies, including the larger ALLHAT, which found that the calcium channel blocker amlodipine was not superior to the diuretic chlorthalidone in reducing the rate of coronary heart disease or stroke and was associated with a higher rate of heart failure, the authors concluded that CONVINCE showed the calcium channel blocker is no better than the diuretic. They believe these data, combined with other completed studies, support the recommendation of the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure for low-dose diuretic (or possibly β-blocker) therapy for hypertensive patients for whom there are no indications that another antihypertensive agent should be used.