Clinical Outcomes in the Diabetes Cohort of the International Verapamil SR-Trandolapril Study

Abstract

Abstract-TheA dults with diabetes are 2 to 4ϫ more likely to die from heart disease and stroke than those without diabetes. This risk increases for adults with hypertension (HT) and diabetes. 1 To reduce cardiovascular risk in those with diabetes, more aggressive blood pressure (BP) control is needed compared with the general population. The sixth report of the Joint National Committee (JNC VI) recommended a target BP of Ͻ130/85 mm Hg for persons with diabetes, and the seventh report (JNC 7) recommends a target of Ͻ130/80 mm Hg. 2,3 Postmyocardial infarction studies demonstrate that ␤-blockers and diuretics, alone or in combination, reduce cardiovascular mortality in coronary artery disease (CAD), with ␤-blockers being preferred. 2,4 However, use of ␤-blockers or diuretics is associated with metabolic abnormalities, including impaired glucose tolerance, insulin resistance and hypokalemia, and increased risk for new-onset diabetes. [5][6][7][8][9] Nondihydropyridine calcium antagonists (non-DHPCAs) such as verapamil SR are recommended as an alternative to ␤-blockers for angina relief in persons with CAD-HT. 2,3 Verapamil SR effectively reduces BP 10 and clinical outcomes in patients with CAD. 11 Moreover, non-DHPCAs are generally considered metabolically neutral. 7,10 Previous outcome studies evaluated the effect of BP reduction with different antihypertensive medications in a cohort of established CAD and HT but without concomitant use of renin-angiotensin system (RAS) blockers (ie, angiotensin-converting enzyme [ACE] inhibitors and angiotensin receptors blockers [ARBs]) and lower BP goals. The INternational VErapamil SR-Trandolapril study (INVEST) evaluated 2 recommended antihypertensive regimens in a CAD-HT population, 2 with the option of adding an ACE inhibitor or hydrochlorothiazide (HCTZ), to achieve JNC VI BP targets. 12 This prespecified analysis reports outcomes in the cohort with diabetes.

Blood Pressure Control and Improved Cardiovascular Outcomes in the International Verapamil SR-Trandolapril Study

“…Finally they show that, although the proportion of visits with BP control and the mean BP level during the treatment period were related to each other, the incidence of fatal and nonfatal cardiovascular events was independently associated with either variable. Our data confirm the results from other studies [1][2][3][4][5][6][7][8][9][10][11] that the extent to which antihypertensive treatment protects hypertensive patients from cardiovascular disease is associated with the mean BP level achieved during treatment, with lower rates of events when a mean BP Ͻ140/90 mm Hg is achieved. A new finding, however, is that an additional factor seems to be how often during the treatment period BP achieves adequate control.…”

“…[1][2][3][4] Second, regardless of the treatment used, in diabetic or other high-risk individuals, cardiovascular protection is greater if on-treatment BP values Ͻ130/80 mm Hg are achieved. [5][6][7][8][9] Third, there is a type of treatment-independent relationship between the magnitude of the mean BP change throughout the treatment period and the incidence of cerebrovascular and coronary events. 10,11 Analysis of BP control using mean follow-up BP does not provide a complete picture of BP control during a study, because BP may be in control at one visit and not in control at the next visit or vice versa.…”

The Challenge of Sudden Death in Dialysis Patients

“…Inhibitors of the opening of these cardiac K ATP channels interfere with ischemic preconditioning of the heart and have been claimed to increase cardiac risk, although recent observational data appear reassuring (82,83). Possibly the absence of ␤ blocker therapy might have been a predisposing factor, although in nonrenal patients, verapamil (which the patient received) was equivalent to ␤ blockers in diabetic patients with coronary heart disease patients (84). So I cannot see what else in the management of this case could have prevented this all-too-common catastrophe.…”

How early should blood pressure control be achieved for optimal cardiovascular outcomes?

“…The studies discussed above and others [22][23][24] illustrate that substantial BP reductions and control rates are indeed attainable within 6 months or sooner. The recently published results of the Avoiding Cardiovascular events through COMbination therapy in Patients LIving with Systolic Hypertension (ACCOMPLISH) trial provide further evidence in this regard, both for the general hypertensive population and for patients with diabetes.…”