Michael E. Cobble, MD, AAFP, FNLA Director, Canyons Medical Center, Adjunct Faculty, University of Utah School of Medicine, Sandy, UT, Chief Medical Officer, Atherotech, Birmingham, AL
References
Further support for treating with statin doses higher than those recommended for initial therapy comes from a prospective trial involving 1337 consecutive patients followed over a median of 33 months.10 Although 83% of these patients were on statin therapy, only 51% had an LDL-C <100 mg/dL, and only 15% of the very high-risk patients (n = 941) had an LDL-C <70 mg/dL. The use of intensive statin therapy was associated with a 12-fold higher possibility of achieving an LDL-C <70 mg/dL. Very high-risk patients who achieved an LDL-C <70 mg/dL had a significantly lower risk of all cardiovascular events (HR, 0.34; P = .003).
Blood pressure
As with dyslipidemia, the cardiovascular benefits of lowering elevated BP are well established. While the usual BP goal is <140/90 mm Hg, in those with hypertension and concomitant diabetes or renal disease, the goal is <130/80 mm Hg.38 It is not clear how best to achieve these goals, but therapy must be individualized based on patient comorbidities and drug side effects as recommended in current guidelines.38-40 With these guidelines as a basis, a simplified ABCD approach can be considered in selecting initial antihypertensive therapy (FIGURE 3).
FIGURE 3
ABCD approach to initial antihypertensive therapy38-40
ACE-I, angiotensin converting enzyme inhibitor; ARB, angiotensin receptor blocker; MI, myocardial infarction. Monotherapy, however, does not result in BP control in most patients. As shown by the Antihypertensive Lipid-Lowering Treatment to Prevent Heart Attacks Trial (ALLHAT), BP control typically requires at least 2 different classes of drugs, with 3 or more drugs required in about 1 in 6 patients within 3 years and 1 in 4 patients within 5 years. A higher percentage of patients with diabetes mellitus or kidney impairment (creatinine ≥1.5 mg/dL) require 3 or more antihypertensive drugs after 5 years (33% and 40%, respectively).41
Several meta-analyses have been conducted recently to assess the magnitude of BP (systolic/diastolic) lowering in the different classes of antihypertensive drugs. While these meta-analyses have important limitations, such as differences in study design and the lack of a clear description of outcomes, some general impressions can be made. In 1 meta-analysis, thiazide diuretics were found to lower BP by 6/3 and 8/4 mm Hg at doses of 1 and 2 times the recommended starting dose, respectively. A BP-lowering effect of 6/3 mm Hg was observed with starting doses of loop diuretics.42 Another meta-analysis failed to find a statistically or clinically significant BP-lowering effect with potassium-sparing diuretics at low doses.43 For spironolactone, a review of 5 crossover studies found a reduction in BP of 21/7 mm Hg. In this review, daily doses of 25 to 100 mg were found to provide the best balance between BP reduction and safety and tolerability.44
Several meta-analyses of angiotensin receptor blockers (ARBs) have found BP reductions to be similar among the various ARB drugs. Generally, at maximum recommended doses, a BP reduction of 8/5 mm Hg is observed with these drugs, except for losartan, which produces a smaller BP reduction.45-49 Heran et al45 found a BP reduction of 12/7 mm Hg among the ARBs 1 to 12 hours after the dose was taken. When cost per quality-adjusted life-year gained was considered, 1 meta-analysis found that the slightly greater BP reduction with candesartan compared with losartan was not cost-effective.46 However, other benefits of candesartan compared with losartan therapy (eg, lower risk for cardiovascular disease, heart failure, dysrhythmias, and peripheral artery disease) should be considered.50 Adverse events were generally found to be similar among the ARBs.
No differences in BP lowering were observed among 92 trials of 14 different angiotensin-converting enzyme inhibitors. As a class, these drugs were found to produce a reduction in BP of 8/5 mm Hg.51
Because of the modest BP-lowering effects of each of the antihypertensive drugs currently available, consideration should be given to starting antihypertensive therapy with 2 agents for patients with stage 2 hypertension (ie, BP ≥160/100 mm Hg).
Summary
Elimination of key risk factors such as dyslipidemia and hypertension is important for reducing cardiovascular events later in life. A medical history, physical examination, and laboratory determination of lipid and glycosylated hemoglobin levels provide a good assessment of cardiovascular risk. A statin is first-line therapy for reducing LDL-C, which is the primary lipid target in most patients. High-dose statin therapy may be required to reach desired target levels. The choice of initial antihypertensive therapy is based on patient comorbidities and drug side effects; however, most patients require combination antihypertensive therapy to reach goal. The combination of this multifactorial risk approach along with smoking cessation and modification of other risk factors should complement current and future cardiovascular care for men.
