Antihypertensive regimen

What is the proper antihypertensive regimen?

With the epidemics of obesity, diabetes mellitus, and CKD, nearly all patients with hypertension will need multiple medications, and many will require three or more medications. The JNC 8 recommends that non-African American hypertensive patients with or without diabetes mellitus begin therapy with either an ACE inhibitor, ARB, calcium channel blocker, or thiazide-type diuretic, while African American hypertensive patients with or without diabetes mellitus begin therapy with either a thiazide-type diuretic or a calcium channel blocker. All hypertensive CKD patients, regardless of diabetic status or race, should begin therapy with either an ACE inhibitor or ARB. The first goal for physicians is to bring their patients’ BPs under good control as quickly as possible, as prompt BP control reduces cardiovascular risk. Data from the Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial suggest that BP control should be achieved no later than 6 months after treatment begins. Many patients will already be on complex medication regimens, and fixed-dose combination pills may be more effective in achieving control than using a multiple-pill approach. Nonpharmacologic management, such as sodium restriction, exercise, smoking cessation, and weight loss, should be emphasized. The aforementioned program should be coupled with regular home BP monitoring.

ACE inhibitors and ARBs merit special attention. They are not appropriate for pregnant women or women planning to become pregnant and those with hyperkalemia, liver cirrhosis, or volume depletion. Serum creatinine and potassium should be checked within a week or two of starting either medication or increasing the dose. Labs should be followed periodically thereafter. Patients prone to hyperkalemia (e.g., diabetics) should be given dietary education. Nonsteroidal medications should be discontinued. Creatinine increases within 30% of baseline levels have traditionally been considered acceptable if unaccompanied by volume depletion and symptomatic hypotension. A recent cohort study of over 120,000 British patients calls into question this arbitrary cutoff, which was determined from clinical trials from the 1990s. Patients in this study who were prescribed either ACE inhibitors or ARBs and whose creatinine levels increased at least 30% from baseline within 2 months of treatment were at significantly higher relative risk for ESKD (243%), myocardial infarctions (46%), heart failure (37%), and death (84%) compared to those patients whose creatinine levels increased <30%. However, many patients whose creatinine levels increased <30% from baseline were also at significant risk: patients whose creatinine levels increased only 10% to 19% experienced higher relative risks for ESKD (73%), myocardial infarctions (12%), heart failure (14%), and death (15%) compared to patients whose creatinine levels increased <10%. Physicians must closely follow their patients’ kidney function while on these medications and consider the risks and benefits of continuing them in the context of even small creatinine elevations. Certainly, the combination of ACE inhibitors and ARBs is no longer recommended. Spironolactone in combination with either an ACE inhibitor or ARB can reduce proteinuria, though this combination can cause significant hyperkalemia, and a beneficial effect on hard endpoints has not been demonstrated.

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