Verapamil treatment lowers diabetes risk
INVEST shows benefits of verapamil-trandolapril combination
A treatment regimen anchored on a calcium antagonist slashes the risk of new-onset diabetes better than a beta-blocker-based strategy among hypertensive patients at high risk of developing the disease.
This was among the significant findings in the landmark International Verapamil SR/Trando-lapril Study (INVEST), which compared verapamil-based and atenolol-based treatment strategies. Published in the Journal of the American Medical Association, the study tracked for two to five years a total of 22,576 patients, 11,267 of whom were assigned to verapamil or verapamil plus ACE inhibitor trandolapril, while 11,309 were assigned to atenolol or atenolol plus hydrochlorothiazide. The study had both diabetic and nondiabetic patients.
The results showed that nondiabetic patients in the verapamil-based treatment group were 15 percent less likely to develop diabetes than those who received the beta-blocker atenolol and the diuretic hydrochlorothiazide (RR = 0.85, 95-percent confidence interval), said Dr. Carl J. Pepine, chief of cardiovascular medicine at University of Florida and principal study author.
Of the 8,098 nondiabetic patients given either verapamil or verapamil plus trandolapril, 569 (7.03 percent) developed new-onset diabetes compared with 665 (8.23 percent) of the 8,078 patients given atenolol or atenolol plus diuretic.
The greater benefit appeared to ensue from the verapamil-trandolapril combination as against the atenolol-hydrochlorothiazide tandem. Explaining the findings during a symposium in Manila last year, Prof. Rainer Kolloch, head of the department of medicine at the University of Munster's Gilead Medical Center in Germany, said the addition of an ACE inhibitor to verapamil results in a dose-dependent reduction in diabetes risk. If the same ACE inhibitor were added to a beta-blocker, the protection is not as potent. On the other hand, adding a diuretic to either regimen hikes the risk for new-onset diabetes.
"The data indicate that the use of trandolapril reduces the risk of new-onset diabetes in the verapamil-based strategy while hydrochlorothiazide increases the risk in both strategies," explained Kolloch.
And for patients who were already diabetic, the verapamil-based regimen offers the same protection against the occurrence of cardiovascular events (death from all causes, nonfatal myocardial infarction, and nonfatal stroke).
A subanalysis of INVEST published in Hypertension in November showed no significant difference in the primary outcomes between the two treatment arms.
Of the total participants in INVEST, 6,400 had diabetes at entry. The authors compared by outcomes in the diabetes cohort (3,169 patients in the verapamil arm and 3,231 in the atenolol arm). A total of 913 participants with diabetes experienced a cardiovascular event with no significant difference between the two treatment strategies--14.6 percent with verapamil as against 13.9 percent with atenolol. They noted, however, that the risk for a cardiovascular event increased with presence of heart failure at baseline, renal impairment, United States residency, age, previous stroke or transient ischemic attack, previous myocardial infarction, peripheral vascular disease, and smoking.
"All hypertensive patients are at risk for diabetes, but patients who had diabetes when they entered the trial had almost a twofold risk in the primary outcome, which was death, heart attack, or stroke," said Pepine. "What that means is once a patient with hypertension and coronary disease has those problems, and then they develop diabetes, it imparts double the risk of having those events. Patients who develop diabetes are very important because it immediately takes them into a very high-risk group."
Moreover, a significantly lower percentage of patients in the verapamil arm (23.2 percent) versus the atenolol arm (24.7 percent) were using antidiabetic medicines after 24 months of treatment (p = 0.04).
"A verapamil SR-based antihypertensive treatment strategy is an alternative to a beta-blocker-based strategy in adults with coronary-artery disease and diabetes," the authors said.
No difference in primary outcomes was also seen in the nondiabetic group.
Both treatment arms achieved comparable reductions in blood pressure. At the end of 24 months, 72 percent of patients in the verapamil arm and 71 percent in the atenolol arm achieved blood-pressure levels of less than 140/90 mm Hg, a target set based on the Sixth National Committee on Hypertension (JNC 6) guidelines of the US Heart, Lung, and Blood Institute.
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