STOCKHOLM -- An antihypertensive combination of amlodipine plus perindopril was strikingly superior to a combination of atenolol and a thiazide diuretic in a major study that followed nearly 20,000 patients for 5.5 years.
The Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) "is a huge study and a big deal," commented Kenneth A. Jamerson, M.D., professor of medicine and a hypertension specialist at the University of Michigan in Ann Arbor.
The combination of the calcium-channel blocker amlodipine (Norvasc) and the ACE inhibitor perindopril (Aceon) "not only led to fewer cardiovascular events, but it also saved lives."
The ASCOT results "should make us rethink what we recommend" for blood pressure lowering, Dr. Jamerson told this newspaper.
"The results will influence clinical practice," commented Salim Yusuf, M.B., professor of medicine at McMaster University in Hamilton, Ont.
The results showed a coherence of data in favor of amlodipine, and are also consistent with those from other studies, he said.
The ASCOT study was stopped prematurely in October 2004 because of the significantly higher mortality among patients randomized to the atenolol-based regimen as well as worse outcomes on several secondary measures.
When all the data were tallied, all-cause mortality occurred at a rate of 13.9 per 1,000 patient-years in the amlodipine group and 15.5 per 1,000 patient-years in the atenolol group, an 11% relative reduction in favor of amlodipine that was statistically significant, Bjorn Dahlof, M.D., reported at the annual congress of the European Society of Cardiology.
Cardiovascular mortality was cut from a rate of 6.5 per 1,000 patient-years in the atenolol group to 4.9 per 1,000 patient-years in the amlodipine group, a 24% relative reduction that was also statistically significant.
The ASCOT results appeared to sharply break from those of ALLHAT (the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack trial), which in a 2002 report showed that a calcium channel blocker or an ACE inhibitor was no better than the diuretic chlorthalidone for preventing events in patients with hypertension in 2002.
But experts pointed to major differences between the two studies. First, the patients enrolled into ASCOT had a much lower baseline risk for cardiovascular events than did those who were enrolled into ALL-HAT, said Peter S. Sever, M.B., an ASCOT coinvestigator and professor of clinical pharmacology and therapeutics at Imperial College in London.
Second, the ALLHAT study was designed to compare individual drugs, while ASCOT was designed to compare two forms of combination therapy, according to Dr. Jamerson.
ASCOT enrolled 19,342 patients with hypertension in the United Kingdom and five other northern European countries during 1998-2000.
Patients were eligible if they were 49-79 years old and had at least three of these cardiovascular risk factors: male gender, age of at least 55 years, smoking, total- to HDL-cholesterol ratio of at least 6, family history of premature coronary heart disease, left ventricular hypertrophy, type 2 diabetes, peripheral artery disease, or prior stroke or transient ischemic attack. …