The past year was a big one in hypertension. A number of trials were reported at meetings and in the medical literature with great potential for changing clinical practice. Studies looking at treatment goals, benefits (or lack thereof) of particular antihypertensive drug classes, and new approaches to reducing cardiovascular risk were published. Several were highly controversial and contrary to the conventional wisdom. Discussion has been sharp and spirited, and will stimulate more studies and further advances in our understanding of high blood pressure and its treatment.
How old is too old for blood pressure treatment? That question was examined in HYVET (Hypertension in the Very Elderly Trial). In this study otherwise healthy octogenarians primarily from North Africa, China and southern Europe were treated with perindopril and/or a diuretic or simply followed. The group treated more aggressively had an impressive reduction in death, heart attack and stroke. The trial suggests you're never too old to benefit from good control of high blood pressure.
Cardiologists by and large prefer inhibitors of the renin-angiotensin system as first line treatment for hypertension. These drugs include ACE (angiotensin converting enzyme) inhibitors and ARBs (angiotensin receptor blockers. In patients with vascular disease, chronic kidney disease and diabetes these drugs have been shown to reduce progression of kidney malfunction, heart attack and stroke. Unfortunately these drugs are not particularly potent blood pressure lowering agents. Most patients require additional blood pressure lowering to achieve modern targets. What is the optimal second drug? ACCOMPLISH (Avoiding Cardiovascular events in Combination Therapy in Patients Living with Systolic Hypertension) examined this question. This trial was reported at the American College of Cardiology annual session and subsequently published in the New England Journal of Medicine. The study randomized patients to a regimen of ACE inhibitor plus diuretic versus ACE inhibitor plus amlodipine (a calcium channel blocker formerly marketed as Norvasc). The study was stopped early because the ACE inhibitor/ amlodipine group experienced 20% reduction in risk for death or cardiac event. Current guidelines recommend diuretics as add-on therapy and this study will certainly provoke a re-examination of the guidelines.
A landmark trial published in the 1990s showed that ACE inhibitors prevented vascular events in diabetics and patients at high risk for vascular disease. Many physicians use ARBs (angiotensin receptor blockers) as equivalent agents for vascular protection. No large studies had examined this purported equivalence. ONTARGET randomized over 25,000 patients to the ACEI ramipril (the drug used in HOPE, the landmark trial mentioned above), the ARB telmisartan or their combination, and followed them for a mean of 55 months. The three regimens afforded similar vascular protection. The combo ACEI/ARB group had more side effects without additional benefit.
Diabetic patients have very high rates of heart attack, stroke and kidney failure. Studies have previously shown that cholesterol lowering with statins and aggressive blood pressure control can reduce risk. Although most physicians stress the importance of glucose control in diabetes, it's not clear that lowering blood sugar reduces risk. Some of the most controversial trials reported this year looked at the impact of blood glucose control on the progression of vascular disease-with surprising results. Three trials reported at the American Diabetes Association annual meeting in San Francisco in June found no significant benefit of aggressive glucose lowering on vascular events. In one of them (ACCORD) the risk for death was actually increased. The others (ADVANCE and VADT) showed no benefit. The role of glucose lowering in prevented heart attack and stroke remains undefined.
Aggressive blood pressure control and cholesterol lowering does save lives in patients with diabetes. SANDS (Stop Atherosclerosis in Native Diabetics Study) looked at lowering blood pressure even further than the 120-130 systolic currently recommended by the guidelines and the current LDL cholesterol ("bad" cholesterol) target of 100 mgs/dl. In that study patients who achieved a blood pressure target of 115 systolic and a LDL cholesterol of less than 70 mgs/dl had less progression of atherosclerosis.
Data presented in these and many other trials this year have sharpened our focus in matching the patient to the agent and to the treatment goal. 2009 will certainly provide more insight and lead to better care for our patients.
Published On: January 06, 2009