Tight control of systolic blood pressure (SBP) to a target of less than 130 mmHg in diabetics with coronary artery disease (CAD) does not significantly reduce the incidence of cardiovascular (CV) events compared with usual control, and is associated with increased all-cause mortality, shows an analysis of INVEST.

In INVEST (International Verapamil SR ??” trandolapril Study), patients with diabetes and CAD were randomly assigned to receive antihypertensive therapy with either a calcium-channel blocker or a beta blocker, plus an ACE inhibitor and/or a thiazide diuretic. In extended follow-up of 6400 patients enrolled in the trial, those who achieved SBPs lower than 130 mmHg had cardiovascular outcomes equivalent to those who achieved SBPs between 130 and 140 mmHg.

But a subanalysis of 5077 patients from the USA showed that the tight BP control strategy was associated with an adjusted hazard ratio (HR) of 1.15 (p=0.036) for all-cause mortality compared with usual control, defined as a SBP lower than 140 mm Hg.

“We wonder whether it’s time to rethink lower BP goals in patients with diabetes and CAD,” said Rhonda Cooper-DeHoff from the University of Florida in Gainesville, Florida, USA, who presented the data during a late-breaking clinical trials session at the 2010 annual scientific sessions of the American College of Cardiology in Atlanta, Georgia, USA.

The findings appear to contravene the position of the American Diabetes Association, which has previously issued a position statement saying that “there is no threshold value for BP [in diabetics], and risk continues to decrease well into the normal range.”

INVEST was designed to determine whether lowering SBP below 130 mmHg could provide additional CV benefits, particularly among diabetic patients with CAD. The international trial enrolled 22,576 patients with CAD and hypertension, and randomly assigned them to receive either verapamil SR plus trandolapril and the thiazide diuretic hydrochlorothiazide [HCTZ], or atenolol plus HCTZ and trandolapril. Trandolapril was recommended for all diabetic patients in the study.

The analysis focused on mortality rates among a US cohort of diabetic patients followed for an extended period, from September 1997 through November 2008. To evaluate the effects of very low SBP, the authors further categorized on-treatment SBP in increments of 5 mmHg.

During the extended follow-up period of 22,700 patient-years, the investigators found that, as predicted, patients whose BP was not controlled on therapy had an approximately 50% higher risk for a composite endpoint of death, nonfatal myocardial infarction (MI) or nonfatal stroke compared with those in the usual-control group. There were no significant differences between the tight- or usual-control groups with regard to either nonfatal MI of nonfatal stroke.

But in a Cox regression analysis of all-cause mortality, both the 110 to less than 115 mmHg and the less than 110 mmHg SBP categories were associated with increased risk for death. Other factors associated with increased mortality risk were age, race, peripheral arterial disease, coronary heart failure, US residency, renal impairment, left-ventricular hypertrophy, and transient ischemia.

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010

Meeting website

Intensive blood pressure (BP) control does not reduce the rate of cardiovascular (CV) events in patients with Type 2 diabetes and high CV risk, reveals research presented at the 59th Annual Scientific Sessions of the American College of Cardiology in Atlanta, Georgia, USA.

The Action to Control Cardiovascular Risk in Diabetes (ACCORD) Blood Pressure trial found that targeting therapy in such patients to achieve a systolic blood pressure (SBP) below 120 mmHg did not significantly reduce the annual rate of a composite of nonfatal myocardial infarction, nonfatal stroke, or death from CV causes, compared with a standard blood pressure target of below 140 mmHg.

A total of 4733 patients aged an average of 62.2 years with Type 2 diabetes were randomly assigned to intensive BP control (n=2362) or standard BP control (n=2371). The patients had an average baseline SBP of 139 mmHg, ranging from 130 to 180 mmHg, and had stable diabetes for at least 3 months, with a HbA1c of 7.5% to 11.0%. Also, 33.7% of patients had CV disease (CVD), while the remainder had subclinical CVD or at least two risk factors.

Patients in the intensive group were initiated on a two-drug therapy, typically a thiazide-type diuretic plus ACE inhibitor, angiotensin receptor blocker, or beta blocker. Drugs were then added and/or titrated at monthly visits to achieve the target SBP of 120 mmHg. In the standard group, therapy was intensified if SBP was 160 mmHg or above at the first visit or 140 mmHg or above at the second visit.

William Cushman, from the Veterans Affairs Medical Center in Memphis, Tennessee, USA, noted that “the SBP separated very early.”

He reported that BP from a year onward averaged at about 134 mmHg for the standard therapy group and at about 119 mmHg for the intensive therapy group.

This meant that, on average, a delta difference in BP of 14 mmHg was achieved from 1 year to the end of the 4.7-year study, which Cushman said was “certainly far greater” than the 10 mmHg minimum that they had set out to achieve.

Patients in the intensive treatment group took more drugs over the course of the study than did those in the standard treatment group, at an average number of 3.4 versus 2.1. Despite the difference in SBP, the patients receiving intensive BP-lowering therapy had a similar risk for the primary outcome as patients receiving standard therapy, at rates of 1.87% and 2.09%, respectively, and a hazard ratio of 0.88 (p=0.20).

The findings, published simultaneously advance online by the New England Journal of Medicine, did show about a 40% reduction in the risk for stroke in the intensive therapy group compared with the standard therapy group, however. And although this finding is consistent with meta-analyses summarizing the impact of a 10-mmHg reduction in SBP on stroke in observational studies, Cushman pointed out that the overall rate of stroke was very low, at about 0.5% per year.

“Therefore, although intensive management did significantly reduce total stroke and nonfatal stroke, assuming that this finding is real… the number needed to treat to lower the SBP to prevent one stroke over 5 years was 89.”

Cushman cautioned that patients receiving intensive therapy were also at increased risk for complications attributed to antihypertensive treatment compared with those receiving standard therapy, with occurrences seen in 3.3% versus 1.3% of patients. But overall serious adverse events were of a low order.

He concluded: “The results find no conclusive evidence that the intensive BP control strategy reduces the rate of a composite of major CV events, which was all-cause or fatal CV events plus nonfatal myocardial infarction and nonfatal stroke in high-risk adults with Type 2 diabetes.”

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010

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