Physician's Weekly Article - Conference Highlights: The ACC/SCAI 2008 Annual Meeting

       The American College of Cardiology and the Society for Cardiovascular Angiography and Interventions held their 2008 annual meeting in Chicago. The news items below are just some of the highlights of emerging news from the meeting. For more information on these items and other research that was presented, go to http://acc08.acc.org.

      HYVET

      The Particulars: Hypertension in the Very Elderly Trial. In patients aged 80 and older, the benefit-to-risk ratio has not been established with regard to treating hypertensive individuals, and current guidelines do not provide clear direction. HYVET was a randomized double-blind placebo-controlled trial involving 3,845 patients aged 80 and older with a systolic blood pressure between 160 mm Hg and 199 mm Hg. The treatment assessed was 1.5 mg of indapamide sustained release with the addition of 2 mg to 4 mg of perindopril (as required) to reach a target blood pressure of less than 150/80 mm Hg versus placebo.

      Data Breakdown: At an average follow-up of 2 years, 48% of patients aged 80 and older taking medication had achieved the target blood pressure of 150/80 mm Hg. In patients who were followed up for longer durations, a greater number of those receiving active treatment achieved the target blood pressure. Patients receiving medications had a 39% reduction in the rate of fatal strokes, a 64% decrease in the rate of fatal and non-fatal heart failure, and a 34% lower risk of cardiovascular events. In July 2007, HYVET was stopped early because of the observed reductions in the primary endpoint and total mortality.

      Take Home Pearls: Many patients aged 80 and older could benefit greatly from treatment for hypertension. Treatment led to reduced risks of fatal strokes, cardiovascular events, and all-cause mortality.

      ONTARGET

      The Particulars: Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial. ONTARGET evaluated telmisartan, an angiotensin receptor blocker (ARB), and ramipril, an ACE inhibitor. Investigators also analyzed if a combination of telmisartan plus ramipril was more effective at reducing risks of cardiovascular death, myocardial infarction (MI), stroke, or hospitalization for heart failure than using ramipril alone. The study enrolled 25,620 patients over age 55 with coronary artery disease or diabetes plus additional risk factors, but who did not have any evidence of heart failure.

      Data Breakdown: When compared with ramipril recipients, average blood pressures were lower in the telmisartan group and the combination group. At 56 months follow up, telmisartan was equal to ramipril with regard to primary outcomes. When compared with the ramipril group, the telmisartan group had lower rates of cough and angioedema, but this benefit was partially offset by a higher rate of hypotensive symptoms. Combination therapy correlated with reductions in systolic blood pressure of 2 mm Hg to 3 mm Hg beyond that seen in the ramipril group, but no significant benefit was seen in composite endpoints for those receiving this therapy.

      Take Home Pearls: Telmisartan lowered blood pressure to a slightly greater extent than ramipril, and combined use of these agents lowered it even further. When used alone, telmisartan and ramipril were equally effective in reducing risks of cardiovascular death, stroke, MI, or hospitalization for heart failure. However, despite further reducing blood pressure, combination therapy failed to offer any additional benefit.

      PERISCOPE

      The Particulars: Pioglitazone Effect on Regression of Intravascular Sonographic Coronary Obstruction Prospective Evaluation. PERISCOPE compared the effects of two different classes of oral glucose-lowering agents on the rate of progression of coronary atherosclerosis in patients with diabetes, as measured by coronary intravascular ultrasound (IVUS). Patients were randomly assigned to receive pioglitazone, a thiazolidinedione (TZD), or glimepiride, a sulfonylurea. TZDs reduce blood glucose primarily by increasing insulin sensitivity whereas sulfonylureas lower blood glucose by acting as insulin secretagogues. Disease progression was measured by repeat IVUS.

      Data Breakdown: An absence of progression of coronary plaque buildup was observed among pioglitazone recipients (-0.16%), compared with highly significant progression with glimepiride (+0.73%). Pioglitazone was associated with more favorable findings regarding biochemical effects, including levels of HDL cholesterol, triglycerides, C-reactive protein (CRP), A1C levels, and blood pressure. Adverse effects were seen in both treatment groups; patients receiving glimepiride experienced more episodes of low glucose levels or angina whereas those receiving pioglitazone experienced more edema and fractures.

      Take Home Pearls: Pioglitazone appears to be more effective than glimepiride in reducing the progression of coronary artery disease in patients with diabetes. When compared with glimepiride, pioglitazone also had a favorable impact on HDL cholesterol, triglycerides, CRP, and A1C. Further studies aimed at studying specific clinical differences between the drug classes are warranted to better define optimal treatment strategies.

      ACCOMPLISH

      The Particulars: Avoiding Cardiovascular Events Through Combination Therapy in Patients Living with Systolic Hypertension. ACCOMPLISH evaluated cardiovascular outcomes using single pill, fixed-dose combination therapy for the treatment of high-risk hypertensive patients. Investigators examined the combination of amlodipine/benazapril, an ACE inhibitor and a calcium channel blocker (CCB), and compared it with hydrochlorothiazide/benazapril, an ACE inhibitor paired with hydrochlorothiazide, to assess the ability of these combinations to reduce cardiovascular morbidity and mortality. The study examined 11,462 patients with high cardiovascular risk and assessed endpoints of mortality, stroke, myocardial infarction (MI), coronary revascularization, unstable angina, and resuscitation from death.

      Data Breakdown: Systolic blood pressure was 0.7 mm Hg lower with ACE inhibitor/CCB combination than with the ACE inhibitor/hydrochlorothiazide combination. Target blood pressure was achieved in 81.7% of patients in the ACE inhibitor/CCB arm compared with a 78.5% rate for the ACE inhibitor/hydrochlorothiazide arm. A 20% reduction in the primary endpoints of cardiovascular mortality, stroke, MI, coronary revascularization, unstable angina, and resuscitation from death was observed in the ACE inhibitor/CCB arm when compared with the ACE inhibitor/hydrochlorothiazide arm.

      Take Home Pearls: A single combination therapy using an ACE inhibitor and a CCB (amlodipine/benazapril) appears to be superior to an ACE inhibitor and a hydrochlorothiazide in reducing blood pressure as well as cardiovascular endpoints in patients with high-risk hypertension. These findings are significant in that they challenge current guidelines, which recommend an initial diuretic-based approach to the treatment of hypertension.

      Eugene Braunwald, MD has indicated to Physician’s Weekly that he has received consulting fees and/or honoraria from Astra Zeneca, Bayer AG, Daiichi Sankyo, Merck & Co, Pfizer, and Schering Plough. He has also received research grants from Astra Zeneca, Bayer Healthcare, Beckman Coulter, Bristol Myers Squibb, CV Therapeutics, Eli Lilly, Genentech, Merck & Co., Novartis, Pfizer, Roche Diagnostics, Sanofi Aventis, and the Schering Plough Research Institute.