Combination of Diuretics and Ace Inhibitors may Protect Diabetes Heart Disease

Combination of Diuretics and Ace Inhibitors may Protect Diabetes Heart Disease

In general, calcium-channel antagonists have not been found to have any deleterious metabolic effects, such as glucose intolerance. However, data from both short-term and long-term studies indicate that ACE inhibitors may actually improve insulin sensitivity and decrease the risk of type 2 diabetes. Indeed, in the recent Heart Outcomes Prevention Evaluation trial, there was a 30 percent decrease in the rate of development of diabetes in a cohort of patients with cardiovascular risk factors who were treated with ramipril, an ACE inhibitor. ACE inhibitors may exert these salutatory effects by improving blood flow through the microcirculation to skeletal-muscle tissue or by improving insulin action in mediating glucose transport at the cellular level.


ACE inhibitors, or inhibitors of Angiotensin-Converting Enzyme, are a group of pharmaceuticals that are used primarily in treatment of hypertension and congestive heart failure, in most cases as the drugs of first choice.ACE inhibitors slow the onset of diabetic nephropathy in patients with microalbuminuria and type 1 diabetes. Normotensive, nonalbuminuric diabetics also have a slower onset of nephropathy.

Angiotensin-converting enzyme (ACE) inhibitors are among the most important drugs for treating patients with heart failure. ACE inhibitors are particularly important for patients with diabetes. A large study reported that patients with diabetes who took these drugs had fewer heart attacks and lower overall mortality rates than patients who took other types of high blood pressure medications. ACE inhibitors may also help slow progression of kidney disease, in addition to controlling blood pressure.

In an earlier publication (Journal of the American Medical Association, December 2002), the ALLHAT investigators reported that diuretics were superior in preventing adverse cardiovascular disease outcomes compared with other first-step antihypertensive medications. The current report indicates that this is true not only in hypertensive patients with a normal blood sugar, but in those with diabetes, or an impaired fasting glucose (pre-diabetes).

Researchers at Rush University Medical Center analyzed the data from all of the randomized clinical trials (in which the assignment of initial drugs is based solely on chance, thus balancing the groups regarding other risk factors for diabetes), and have found significant differences between antihypertensive drugs. ACE-inhibitors and the newer angiotensin receptor blockers, or ARBs prevent people from getting diabetes, and the older diuretics or beta-blockers, increase the chance that a person becomes diabetic, compared to either placebo (inactive sugar-pills) or calcium channel blockers according to a study published in the January 20, 2007 issue of The Lancet.

Regardless of race or ethnicity, lowering blood pressure is extremely important in reducing future cardiovascular risk, Cooper-DeHoff ;a research assistant professor and associate director of the clinical research program in cardiovascular medicine, said.

"Even lowering blood pressure two or three millimeters of mercury is associated with significant reduction in the risk of subsequent stroke," she said. "It's very important even for those with mild hypertension to seek treatment. And if we can choose medications in Hispanic patients that reduce the risk of developing diabetes, that's an important thing for physicians prescribing blood pressure-lowering medications to keep in mind."

Angiotensin II has been shown to increase hepatic glucose production and decrease insulin sensitivity. Patients who utilize either an ACE inhibitor (ACEI) or angiotensin receptor blocker (ARB) may experience a decreased incidence of new-onset type 2 diabetes.

If you have chest pain (angina), your doctor may recommend a beta blocker, which can lower your blood pressure and also prevent your chest pain, reduce your heart rate and decrease your risk of death. If you have diabetes and high blood pressure, taking a thiazide diuretic plus an ACE inhibitor can decrease your risk of heart attack and stroke. If you have diabetes, high blood pressure and kidney disease, you may need to add additional medications to the mix, such as an angiotensin II receptor blocker.

Elliot and his colleague Dr Peter Meyer (Rush University Medical Center) note that four independent meta-analyses have shown that direct inhibitors of the renin-angiotensin system reduce the risk of incident diabetes.Elliott commented to heartwire that as the results of this network meta-analysis are broadly in line with what would have been expected, with ARBs and ACE inhibitors showing the best protective effects against diabetes and beta blockers and diuretics the worst diabetic profile, this should enhance confidence in the technique. "Maybe people out there will look to this paper as a reason to use network meta-analyses in other fields," he said.

Using a combination of diuretics and ACE inhibitors to manage blood pressure in people with type 2 diabetes can help protect against heart disease, according to new data released Sunday.

The combined therapy, administered as part of a worldwide study known as ADVANCE, reduced the risk of dying from heart disease by 18 percent.

"If the benefits seen in ADVANCE were applied to just half the population with diabetes worldwide, more than a million deaths would be avoided over five years. For these reasons, there is now a case for considering such treatment routinely for patients with type 2 diabetes," study author John Chalmers, from The George Institute at the University of Sydney in Australia, said in a prepared statement.

By 2030, an estimated 350 million people will be living with diabetes worldwide. Heart disease kills two out of three people with diabetes, who are at increased risk of stroke, heart attacks and related conditions such as degenerative eye disease. Blood pressure management is recommended to reduce the risk of heart disease.

The new findings comes from the ADVANCE trial, which tracked more than 11,100 people with type 2 diabetes from 215 medical centers in 20 countries for four years.

The participants, all 55 or older, received either a combination of the ACE inhibitor perindopril and the diuretic indapamide or a placebo.

Over the course of the four years, the researchers found that people with the combined therapy had an average reduction in systolic blood pressure of 5-6 mm Hg and diastolic blood pressure of 2 mm Hg compared with the placebo group.

People who got the combined therapy were 9 percent less likely to have a heart disease event, such as stroke or heart attack, over the treatment period. They were also 18 percent less likely to die from heart disease and 14 percent less likely to die from any cause.

The researchers noted that the impact of the combined therapy occurred regardless of the participants' blood pressure at the beginning of the study.

The study was released online Sunday by The Lancet to coincide with a presentation of the research at the European Society of Cardiology meeting in Vienna.

In an accompanying commentary in the journal, Dr. Norman Kaplan, a hypertension expert from the University of Texas Southwestern Medical Center at Dallas, had a caution on the findings.

"The fixed combination of perindopril and indapamide could be the best possible protector against hyper-tension-related consequences for patients with type 2 diabetes, but I believe that other drugs, if they lower blood pressure as much and do not have metabolic side-effects, would be as protective as this combination treatment," he said.

And he added, "As has been said many times before by many experts: In most circumstances, lowering the blood pressure is what counts, not the way by which it is lowered."

"Controlling high blood pressure is an urgent concern especially for people with diabetes. Our findings demonstrate the advantages of diuretics in diabetics as well as in those with impaired and normal fasting glucose levels," said NHLBI director Dr. Elizabeth G. Nabel. "As a physician, I have seen the consequences of poorly controlled hypertension and diabetes. These results show many people and their families can be spared that devastation."

Prescribing the right blood pressure medication can be tricky. Some blood pressure medications are not good for people with diabetes or heart disease, for example. Some medications may not be tolerated by some people. Some blood pressure medications just don’t work with some people. Fortunately, there is a wide choice of blood pressure medications. Ask your doctor what type of medication you are taking and what the potential side effects might be. Remember that many of these side effects are not common and many will go away in time. Never suddenly stop taking your medication without consulting your physician.

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