Further information: Hypertension (see p1833) and Endocrine Disorders and the Heart (see p2295) from Cardiovascular Medicine, 3rd Edn*

The 70th Scientific Sessions of the American Diabetes Association (ADA) was held June 25–29, 2010 in Orlando, Florida.  Papers of major significance related to diabetes and cardiovascular disease were presented, and three of the issues that were addressed will be discussed here: blood pressure control in hypertensive diabetics with heart disease, the significant increase in risk of vascular disease in diabetics, and an ongoing controversy over the use of thiazolidinediones, specifically rosiglitazone, for glycemic control in diabetic patients.

Tight Blood Pressure Control and Cardiovascular Outcomes Among Hypertensive Patients with Diabetes and Coronary Artery Disease

This is a subgroup analysis of 6400 participants in the International Verapamil SR-Trandolapril Study (INVEST), a trial that enrolled 22,576 subjects between September 1997 and December 2000 and followed them through 2008.  The current analysis [1] of the patient cohort aimed at determining whether improved cardiovascular outcomes were better achieved by maintaining tight control and lowering systolic blood pressure (BP) to less than 130 mmHg or usual control where BP ranged from 130 mmHg to less than 140 mmHg.  Uncontrolled was considered 140 mmHg or higher.  Results showed that a primary outcome event occurred in 12.7% of patients who had maintained tight control, 12.6% of patients who had maintained usual control, and 19.8% of patients who had uncontrolled systolic BP.  Similarly, in the results for the cardiovascular event rate and the rate for all-cause mortality, little difference existed between participants in the tight control group and those in the usual control group.  Investigators concluded that tight control of systolic BP in diabetic patients with coronary artery disease did not result in improved cardiovascular outcomes over the patients who maintained usual control.  Also on the Cardiovascular Medicine website [2], the results of the ACCORD trial [3] were reported and would be of interest to the reader of this report.  

Diabetes Mellitus, Fasting Blood Glucose Concentration, and Risk of Vascular Disease: a Collaborative Meta-Analysis of 102 Prospective Studies

The June 26, 2010 issue of The Lancet was a themed issue in collaboration with the 70th Scientific Sessions of The American Diabetes Association in Orlando, Florida on June 26–29, 2010.  The following study [4] and accompanying Editorial [5] report on a recent study conducted in an effort to understand the increased risk of vascular disease for diabetic patients.

The strong association between diabetic patients and their elevated risk across the entire gamut of  vascular disease, both ischemic and hemorrhagic, has not been explained by conventional risk factors, such as obesity, blood pressure, lipids, inflammatory markers, or renal function.  Even when those risk factors are controlled, diabetics still have a significant increase in incidence of vascular disease.  In an effort to understand the cause of the increase risk, the Emerging Risk Factors Collaborators conducted a meta-analysis of 102 prospective studies that included data for 698,782 diabetic patients without known vascular disease initially [4].  Combined within-study regressions were adjusted for age, gender, smoking status, systolic blood pressures, and body mass index and used to calculate hazard ratios (HR) for vascular disease. Adjusted HRs for a diabetic’s incidence of coronary artery disease were 2.00 (1.83–2.19), for ischemic stroke were 2.27 (1.95–2.65), hemorrhagic stroke were 1.56 (1.19–2.05), for unclassified stroke were 1.84 (1.59–2.13), and for other vascular deaths were 1.73 (1.51–1.98).  The collaborators also conducted a separate analysis of risk associated with fasting blood glucose concentrations and after evaluating all data and accounting for all relevant risk factors, concluded that diabetic patients carry a two-told risk for the entire range of vascular diseases that are independent of conventional risk factors, including a 56% risk of hemorrhagic stroke.  For people without diabetes, impaired fasting glucose status did not impact risk of vascular disease when combined with information about conventional risk factors.

In an accompanying editorial [5],  Dr. Hertzel Gerstein states that the current study has made a significant contribution to the relationship between fasting glucose and cardiovascular  risk in that the defect regarding glucose is not the only factor to be considered.  There are other abnormalities that might promote cardiovascular disease in diabetic patients, and long-term trials in insulin-replacement therapy that are currently underway might shed more light on the link between diabetes and serious cardiovascular outcomes.

[1] Cooper-DeHoff RM, Gong Y, Handberg EM, et al. Tight blood pressure control and cardiovascular outcomes among hypertensive patients with diabetes and coronary artery disease. JAMA 2010;304:61-8

[2] Effects of combination lipid therapy and intensive blood-pressure control in type 2 diabetes mellitus. http://cardiovascular-medicine.com/?p=231

[3] The ACCORD Study Group. Effects of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med 2010; 362:1575-85

[4] The Emerging Risk Factors Collaboration. Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies. Lancet 2010;375:2215-22

[5] Gerstein HC. More insights on the dysglycaemia-cardiovascular connection. Lancet 2010; 375:2195-6

Note: You may need subscriptions to access content from links on this page. You are responsible for obtaining these subscriptions.

* To view the online text from the book, please navigate to SpringerLink or use the DVD to access electronic content. SpringerLink is a subscription service. For further information, click here.

Further information: Atherosclerosis: Pathogenesis, Morphology, and Risk Factors (see p1593) and Hematologic Disease and Heart Disease (see p2409) from Cardiovascular Medicine, 3rd Edn*

The Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH) trial was conducted to evaluate whether lowering blood levels of homocysteine with folic acid plus vitamin B12 had a protective effect in preventing cardiovascular disease and stroke [1]. Although earlier observational studies [2,3] have indicated that significantly lowering blood levels of homocysteine resulted in lower risk of coronary heart disease (CAD) and stroke, data that showed definite protective effects had not resulted from any of the large-scale randomized trials.

SEARCH was a double-blind randomized trial that enrolled 12,064 survivors of myocardial infarction (MI). The trial was conducted at 88 hospitals in the United Kingdom, and men and women between 18 to 80 years of age with a history of MI were enrolled between 1998 and 2008. Patients were randomized to receive either 2 mg of folic acid plus 1 mg of vitamin B12 or placebo. The primary outcome was a major vascular event, such as coronary death, MI, or coronary revascularization, stroke, or noncoronary revascularization.

During the follow-up period for patients randomized to folic acid plus vitamin B12, major vascular events occurred in 1537 of the 6033 participants (25.5%) vs. 1493 of 6031 (24.8%) of patients on placebo (risk ratio [RR], 1.04; 95% confidence interval [CI], 0.97–1.12; P=0.28). No apparent effects were shown for major coronary events (folic acid/vitamins, 1229 [20.4%], vs. placebo, 1185 [19.6%]; RR, 1.05; 95% CI, 0.97–1.13), stroke (folic acid/vitamins, 269 [4.5%], vs. placebo, 265 [4.4%; RR, 1.02; 95% CI, 0.86–1.21, or noncoronary revascularization (folic acid/vitamins, 178 [3.0%], vs placebo, 152 [2.5%]; RR, 1.18, 95%, CI, 0.95–1.46). No significant differences in numbers of deaths were due to vascular causes (folic acid/vitamins, 578 [9.6%], vs. placebo, 559 [9.3%]) or nonvascular causes (folic acid/vitamins, 405 [6.7%], vs. placebo, 392 [6.5%]).

SEARCH investigators concluded that folic acid/vitamin supplementation did not produce a benefit for major vascular events overall or in any of the subgroups, nor was benefit shown for incidence of stroke prevention.

[1] Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH) Collaborative Group. Effect of homocysteine-lowering with folic acid plus vitamin B12 vs placebo on mortality and major morbidity in myocardial infarction survivors. JAMA 2010;303:2486-94

[2] Clarke R, Daly L, Robinson K, et al. Hyperhomocysteinemia: an independent risk factor for vascular disease. N Eng J Med 1991;324:1149-55

[3] Boushey CJ, Beresford SA, Omenn GS, et al. A quantitative assessment of plasma homocysteine as a risk factor for vascular disease: probable benefits of increasing folic acid intakes. JAMA 1995;274:1049-57

Note: You may need subscriptions to access content from links on this page. You are responsible for obtaining these subscriptions.

* To view the online text from the book, please navigate to SpringerLink or use the DVD to access electronic content. SpringerLink is a subscription service. For further information, click here.

Further information: Endocrine Disorders and the Heart (see p2295) and Cardiovascular Complications of Obesity and the Metabolic Syndrome (see p2693) from Cardiovascular Medicine, 3rd Edn*

Although published in the two separate papers listed above, the effects of Valsartan and Nateglinide were studied in the same trial entitled, “Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR)” [1, 2]. The double-blind, randomized clinical trial with a two-by-two factorial design was conducted from January 2002 through January 2004, with recruitment occurring at 806 centers in 40 countries. Eligible patients had impaired glucose tolerance, a fasting plasma glucose level of at least 95 mg/dl, but less than 126 mg/dl, and one or more cardiovascular risk factors or known cardiovascular disease, and 9306 participants were enrolled. Patients were randomized to receive either nateglinide, up to 60 mg three times a day, or a matching placebo, and valsartan, up to 160 mg daily, or a matching placebo. In addition, patients were required to participate in a lifestyle program, and a goal was set to maintain a 5% weight loss, an increase in physical activity to an average of 30 min five days a week, and adherence to a low-fat diet. Valsartan, an angiotensin-receptor blocker (ARB), is used to treat high blood pressure, heart failure (HF), and long-term consequences of a heart attack. Valsartan was selected for this trial to evaluate the use of an ARB in the delay or prevention of diabetes and to determine the possibility of its helping the cardiovascular system. In the valsartan group, the cumulative incidence of diabetes was 33.1%, as compared with 36.8% in the placebo group (hazard ratio (HR) with valsartan, 0.86; 95% confidence interval [CI], 0.80–0.92; P<0.001). Compared with placebo, valsartan did not significantly reduce the incidence of either the extended CV outcome (14.5% vs. 14.8%; hazard ratio [HR], 0.96; 95% CI, 0.86–1.07; P=0.43) or the core CV outcome (8.1% vs. 8.1%; HR, 0.99; 95% CI, 0.86–1.14; P=0.85). Although nateglinide is in a class of drugs previously shown to lower post prandial glycemia, the hoped-for effect did not occur in NAVIGATOR, nor was the incidence of cardiovascular disease reduced. Nateglinide compared with placebo did not reduce cumulative incidence of diabetes (36% and 34% respectively; HR, 1.07; 95% CI, 1.00–1.15; P=0.05), the core composite CV outcome (7.9% and 8.3% respectively; HR, 0.94, 95% CI, 0.82–1.09; P=0.43), or the extended composite CV outcome (14.2% and 15.2%, respectively; HR, 0.93%, 95% CI, 0.83–1.03; P=0.16).

In an accompanying editorial [3], the author opined that effective lifestyle interventions should be used to combat the current diabetes epidemic, a critical public health concern, but for now, neither drug evaluated in the NAVIGATOR should be used.

[1] The NAVIGATOR study group.Effect of valsartan on the incidence of diabetes and cardiovascular events. N Engl J Med 2010;362(16):1477-90

[2] The NAVIGATOR study group.Effect of nateglinide on the incidence of diabetes and cardiovascular events. N Engl J Med 2010;362(16):1463-76

[3] Navigating the choices for diabetes prevention. Nathan DM. N Engl J Med 2010;362:1533-35

Note: You may need subscriptions to access content from links on this page. You are responsible for obtaining these subscriptions.

* To view the online text from the book, please navigate to SpringerLink or use the DVD to access electronic content. SpringerLink is a subscription service. For further information, click here.

Further information: Hypertension (see p1833) and Endocrine Disorders and the Heart (see p2295) from Cardiovascular Medicine, 3rd Edn*

This review features two studies focusing on patients with diabetes mellitus that were recently presented at the American College of Cardiology Scientific Sessions in Atlanta. Both segments of the ACCORD trial are summarized here.

The Action to Control Cardiovascular Risk in Diabetes (ACCORD) [1] was conducted in diabetic patients who were at high-risk of cardiovascular (CV) events to determine if a combination therapy that included a fibrate to raise HDL cholesterol and to lower triglyceride levels and a statin to lower LDL cholesterol was more effective than treatment with statin therapy alone. Between January 11, 2001 and October 29, 2005, 5518 patients in 77 clinical sites who were already being treated with open-label simvastatin were randomized to also receive either masked fenofibrate or placebo. Prespecified primary outcome was the first occurrence of a major CV event, including nonfatal myocardial infarction (MI), nonfatal stroke, or death from CV causes. Secondary outcomes were a combination of the primary outcome plus revascularization or hospitalization for congestive heart failure (HF), a combination of a fatal CV event, nonfatal MI, or unstable angina; nonfatal MI; fatal or nonfatal stroke; death from any cause or from CV causes; and CV death due to HF. The average follow-up for patients who did not have an event was 5.6 years. There were no significant differences in the primary outcome for either the fenofibrate group (annual rate, 2.2%) or the placebo group (annual rate, 2.4%), with hazard ratio (HR) in fenofibrate group, 0.92; 95% confidence interval (CI), 0.79–1.08; P=0.32. There were also no significant differences in secondary outcomes. Annual rates of death were 1.5% in the fenofibrate group and 1.6% in the placebo group (HR, 0.91; 95% CI, 0.75–1.10; P=0.33). ACCORD investigators concluded that combination therapy did not reduce CV risk in high-risk patients with type 2 diabetes.

This study [2] draws from the same cohort of patients with type 2 diabetes mellitus as the previous paper; however, the focus of this study was to determine if lowering the systolic blood pressure (BP) to less than 120 mm Hg was more effective in reducing CV events than the current target strategy of lowering systolic BP to below 135–140 mmHg. The 4733 patients with type 2 diabetes were randomly assigned to receive intensive therapy that would target a systolic pressure of less than 120 mmHg, or a standard therapy of pressure less than 140 mmHg. The same primary and secondary outcomes were in effect for both ACCORD trials. In the intensive therapy group after one year, the mean systolic BP was 119.3 mm Hg, and in the standard therapy group, mean systolic BP was 133.5 mmHg. In the intensive therapy group, the annual rate of outcome was 1.87%, and it was 2.09% in the standard therapy group (HR with intensive therapy, 0.88; .95% CI, 0.73–1.06; P=0.20). There were no significant differences in annual rates of death. The annual rates of stroke were 0.32% in intensive therapy patients and 0.53% in the standard therapy patients. Of the 2362 patients in the intensive therapy group, 77 had serious adverse events related to antihypertensive treatment (3.3%), as did 30 of 2371 patients in the standard therapy group (1.3%). Investigators concluded that targeting a systolic BP of less than 120 mmHg did not reduce risk of CV events in patients with type 2 diabetes.

[1] The ACCORD Study Group. Effects of combination lipid therapy in type 2 diabetes mellitus. N Engl J Med 2010 (10.1056/NEJMoa1001282)

[2] The ACCORD Study Group. Effects of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med 2010 (10.1056/NEJMoa1001286)

Note: You may need subscriptions to access content from links on this page. You are responsible for obtaining these subscriptions.

* To view the online text from the book, please navigate to SpringerLink or use the DVD to access electronic content. SpringerLink is a subscription service. For further information, click here.

Further information: Pulmonary Arterial Hypertension (see p2203) from Cardiovascular Medicine, 3rd Edn*ESC Clinical Practice Guidelines on Diagnosis and Treatment of Pulmonary Hypertension (2009) (Eur Heart J; doi:10.1093/eurheartj/ehp297)   Full text

Note: You may need subscriptions to access content from links on this page. You are responsible for obtaining these subscriptions.

* To view the online text from the book, please navigate to SpringerLink or use the DVD to access electronic content. SpringerLink is a subscription service. For further information, click here.

Further information: Endocrine Disorders and the Heart (see p2295) from Cardiovascular Medicine, 3rd Edn*

Rosiglitazone was evaluated in the RECORD trial [1] when added to the medication regime of patients using metformin, a sulfonylurea, or both to lower blood glucose in patients with type 2 diabetes. The use of the thiazolidinedione rosiglitazone has been the subject of clinical trials in the past, and the results of the RECORD trial still leave unresolved concerns regarding the safety of the drug.

RECORD was a randomized, open-label, dual-therapy trial conducted at 364 centers in Europe and Australia. A total of 4447 patients were enrolled and were randomly assigned to receive rosiglitazone in combination with either metformin or sulfonylurea (n=2220) or a metformin/sulfonylurea combination (n=2227). The primary endpoint was cardiovascular hospitalization or cardiovascular death, and the hazard ratio non-inferiority margin was 1 to 20.

Rosiglitazone is known to cause fluid retention and possibly heart failure, and in the trial, heart failure resulting in admission to the hospital occurred in 61 patients in the rosiglitazone group and 29 in the metformin/sulfonylurea group, thus further supporting the concern. Limb fracture in women increased as well.

The trial did not produce evidence of the drug’s effect on myocardial infarction, and the investigators concluded that the drug does not increase the risk of overall cardiovascular morbidity or mortality. Therefore, the clinical implications for use of rosiglitazone indicated that it should not be used in heart failure patients and should be used with caution in women at risk of fractures, but it is highly effective in glycemic control for patients with type 2 diabetes when used with care.

[1] Home PD, Pocock SJ, Beck-Nielsen H, et al, Rosiglitazone evaluated for cardiovascular outcomes in oral agent combination therapy for type-2 diabetes. Lancet 2009;373:2125-35

Note: You may need subscriptions to access content from links on this page. You are responsible for obtaining these subscriptions.

* To view the online text from the book, please navigate to SpringerLink or use the DVD to access electronic content. SpringerLink is a subscription service. For further information, click here.

Further information: Endocrine Disorders of the Heart (see p2295) from Cardiovascular Medicine, 3rd Edn*
 
Patients originally studied in the United Kingdom Prospective Diabetes Study (UKPDS) were investigated for post-trial monitoring to determine whether risk reductions for microvascular and macrovascular disease, achieved with the use of improved blood-pressure control during the trial, were sustained [1]. The original trial was performed from 1987–1991, and 5102 patients with newly diagnosed type 2 diabetes mellitus who enrolled in the UKPDS trial were randomly assigned to tight blood-pressure control regimen involving an angiotensin-converting-enzyme (ACE) inhibitor or a beta-blocker, or a less-tight blood pressure control regimen that excluded these mediators.

In the group receiving tight control, there were relative risk reductions of 24% for any diabetes-related end point, 32% for diabetes-related death, 44% for stroke, and 37% for microvascular disease. After a 5-year follow-up, reports from data obtained from patients suggested that there may be a continuing effect of earlier improved management of risk factors. When the trial ended in 1991, patients entered a 10-year post-trial monitoring program, and information was obtained by clinic visits and questionnaires; by years 6–10, funding constraints resulted in the use of questionnaires only. The current paper reports the results of a 10-year, post-interventional follow-up of the survivor cohort of the UKPDS blood-pressure study using data obtained from the documentation of hospitals and general practitioners. The authors examined whether a continued benefit of earlier improved blood-pressure control was evident, and if there were continued benefit, the degree to which it continued.

The report concluded that the benefits of previously improved blood-presssure control were not sustained when blood pressure differences were no longer maintained. Optimal blood pressure control is of major importance in patients with type 2 diabetes and reduces the risks of microvascular and macrovascular disease, if blood-pressure control is maintained.

[1] Holman RR, Paul SK, Bethel A, et al. Long-term follow-up after tight control of blood pressure in type 2 diabetes. N Engl J Med 2008;359:1565-76

Note: You may need subscriptions to access content from links on this page. You are responsible for obtaining these subscriptions.

* To view the online text from the book, please navigate to SpringerLink or use the DVD to access electronic content. SpringerLink is a subscription service. For further information, click here.

Treatment of Hypertension in Patients 80 Years of Age or Older

Further information: Aging and the Cardiovascular System from Cardiovascular Medicine, 3rd Edn*

The age group consisting of persons 80 years of age or older is the fastest growing segment of the general population, and although reduction of blood pressure is considered effective in stroke prevention and other vascular events, guidelines for the treatment of patients 80 years of age or older have been inconclusive as to the benefit achieved, perhaps even suggesting that risks are involved in blood pressure reduction therapy in the older population. A recent meta-analysis of a cohort of patients 80 years or older reported shorter survivals for patients with systolic blood pressures below 140 mmHg after adjustment for known predictors of death. In the Hypertension in the Very Elderly Trial (HYVET), investigators aimed to resolve the areas of uncertainty regarding the relative benefits and risks of antihypertensive treatment in patients 80 years of age or older [1].

To enroll in the trial, patients had to be 80 years old or older with persistent hypertension defined as sustained systolic blood pressure of 160 mm Hg. HYVET was a double-blind, randomized, placebo-controlled clinical trial that enrolled 3845 patients, and the investigators evaluated the effect of stepped-care therapy that began with a patient’s receiving the diuretic indapamide (sustained release, 1.5 mg) or placebo, and may have included the addition of perindopril, angiotensin-converting-enzyme (ACE) inhibitor), or placebo if necessary to attain and maintain the target blood pressure of 150/80 mmHg. Primary end point was fatal or nonfatal stroke. Both the active-treatment group of 1933 patients and the placebo-controlled group of 1912 patients were well-matched.

Active treatment was associated with a 30% reduction in the rate of fatal or nonfatal strokes (95% confidence interval [CI], -1 to 51; P=0.06), a 39% reduction in the rate of death from stroke (95% CI, 1–62; P=0.05); a 21% reduction in the rate of death from any cause (95% CI, 4–35; P=0.02), a 23% reduction in the rate of death from cardiovascular causes (95% CI, -1 to 40; P=0.06), and a 64% reduction in the rate of heart failure (95% CI, 42–78; P<0.001). There were 358 serious adverse events in the active-treatment group (358) vs. 448 adverse events in the placebo group (P=0.001); therefore, the results of HYVET provided evidence of the usefulness of treating hypertension in persons 80 years old or older, as well as providing important guidelines in the treatment of such patients.

[1] Beckett NS, Peters R, Fletcher AE, et al. Treatment of hypertension in patients 80 years of age or older. N Engl J Med 2008;358:1887-98.

Note: You may need subscriptions to access content from links on this page. You are responsible for obtaining these subscriptions.

* To view the online text from the book, please navigate to SpringerLink or use the DVD to access electronic content. SpringerLink is a subscription service. For further information, click here.

Telmisartan and/or Ramipril in Patients at High Risk for Vascular Events

Further information: Endocrine Disorders and the Heart from Cardiovascular Medicine, 3rd Edn*

Investigators from 733 centers in 40 countries conducted the “Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint (ONTARGET)” trial [1], in which 25,620 patients over 55 years of age who had coronary heart disease or diabetes, but had no evidence of heart failure (HF), were enrolled.

The initial phase was a single-blind, run-in phase followed by double-blind randomization of patients into three groups: 8576 received ramipril 10 mg/day, 8542 received telmisartan 80 mg/day, and 8502 received both drugs (combination therapy). The primary aim of the study was to determine the effectiveness of telmisartan 80 mg as compared with ramipril 10 mg/day in reducing mortality or morbidity from cardiovascular causes, and to determine if the combination therapy were more effective than either of the two drugs alone, thus reducing the primary composite outcome of death from cardiovascular causes, myocardial infarction, stroke, or hospitalization for HF. Ramipril is an angiotensin-converting-enzyme (ACE) inhibitor that reduces mortality and morbidity in patients with vascular disease or diabetes without HF, but is not well-tolerated by some patients because of cough, hypotension, or angioneurotic edema. Telmisartan is an angiotensin-receptor blocker (ARB), and the effect of ARBs in such patients is unknown, but ARBs may be better tolerated by patients than ACE inhibitors.

Results showed that in the telmisartan group, mean blood pressure was lower than in the ramipril group by 1 mmHg lower systolic pressure, and the combination therapy lowered blood pressure still further (2 mmHg systolic lower). The combination therapy was associated with higher rate of hypotension-related side effects, including syncope, and potassium levels were decreased.

The investigators concluded that telmisartan is a safe and effective alternative to ramipril and has fewer side effects, but the combination therapy of telmisartan and ramipril should not be used.

[1] ONTARGET Investigators. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med 2008;358:1547-59

Note: You may need subscriptions to access content from links on this page. You are responsible for obtaining these subscriptions.

* To view the online text from the book, please navigate to SpringerLink or use the DVD to access electronic content. SpringerLink is a subscription service. For further information, click here.

Comparison of Pioglitazone and Glimepiride on Progression of Coronary Atherosclerosis in Type 2 Diabetes

Further information: Endocrine Disorders and the Heart from Cardiovascular Medicine, 3rd Edn*

The “Pioglitazone Effect on Regression of Intravascular Sonographic Coronary Obstructive Prospective Evaluation (PERISCOPE)” trial [1] was a prospective, randomized, multicenter, double-blind trial that treated 543 patients with coronary artery disease (CAD) and type 2 diabetes for 18 months at 97 academic centers and community hospitals in America. A primary goal of therapy for diabetics is management of glucose levels, and although the progression of atherosclerosis is especially aggressive in diabetic patients, a diabetic therapy regimen has not been found that reduces the progression of coronary atherosclerosis.

Investigators compared an insulin sensitizer, pioglitazone, with glimepiride, an insulin secretagogue (stimulates insulin release by the pancreas), on the progression of coronary atherosclerosis in patients with type 2 diabetes. At entry, all patients underwent intravascular ultrasonography (IVUS) to measure the amount of plaque volume on the arterial wall, and then were randomized to receive glimepiride, 1–4 mg, or pioglitazone, 15–45 mg, for 18 months and titrated to maximum dosage, if tolerated. At 18 months, a second IVUS examination was performed to determine the amount of change in coronary plaque volume. The primary outcome was the calculation of the change in percent atheroma volume (PAV), an indicator of the progression of coronary plaque buildup.

The principle finding of the study showed no progression of plaque buildup with the use of pioglitazone (–16%) as compared with significant progression of plaque buildup with glimepiride (+0.73%), (P=0.002). Pioglitazone was also more effective in favorably altering levels of high-density lipoprotein (HDL), triglycerides, and C-reactive protein.

After analyzing the data from PERISCOPE, investigators concluded that when compared with glimepiride, the use of pioglitazone resulted in a lower rate in the progression of coronary atherosclerosis.

[1] Nissen SE, Nicholls SJ, Wolski K, et al. Comparison of pioglitazone vs. glimepiride on progression of coronary atherosclerosis in patients with type 2 diabetes: PERISCOPE. JAMA 2008;299:1561-1573

Note: You may need subscriptions to access content from links on this page. You are responsible for obtaining these subscriptions.

* To view the online text from the book, please navigate to SpringerLink or use the DVD to access electronic content. SpringerLink is a subscription service. For further information, click here.