Blood-Pressure and Cholesterol Lowering in Persons without Cardiovascular Disease

Linh Bao Nguyen, Mercer University College of Pharmacy

 

The Eighth Joint National Committee (JNC 8) guideline recommends initiating treatment when blood pressure is higher than 150/90 for patients older than 60. Initiating treatment is recommended for patients younger than 60 when either systolic is higher than 140 or diastolic is higher than 90. Treatment is not recommended when blood pressure is less than 140/90. [1]

The American Society of Hypertension (ASH) recommends drug therapy for patients with blood pressures higher than 140/90. [2]

 

According to the American College of Cardiology/American Heart Association (ACC/AHA), patients 40-75 years of age, without diabetes, and with a low-density lipoprotein level from 70-190 mg/dL are recommended to take a moderate intensity statin. [3]

 

A review of ten studies states that combining cholesterol lowering therapy and blood pressure lowering therapy might prevent about two-thirds to three-quarters of vascular events. [4]

 

Title: Blood-Pressure and Cholesterol Lowering in Persons without Cardiovascular Disease
Design Double-blind, randomized, placebo-controlled trial; N= 12,705
Objective To evaluate the combination of lipid and blood-pressure lowering versus dual placebo in preventing cardiovascular events among persons who did not have cardiovascular disease and who were at intermediate risk
Study Groups Group A: candesartan-hydrochlorothiazide plus rosuvastatin (n= 3,180); Group B: rosuvastatin plus placebo (n= 3,181); Group C: candesartan-hydrochlorothiazide plus placebo (n= 3,176); and Group D: placebo plus placebo (n= 3,168)
Methods Eligible patients received both active treatments for blood-pressure lowering and cholesterol lowering for four weeks. Patients with 80% or more compliance were randomized to receive either lipid and blood-pressure lowering therapies, lipid lowering therapy alone, blood-pressure lowering therapy alone, or placebo. Lipid lowering therapy was rosuvastatin 10 mg once daily. Blood-pressure lowering therapy was candesartan 16 mg plus hydrochlorothiazide 12 mg once daily.
Duration April 2007 to November 2010
Primary Outcome Measure First co-primary outcome: composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke; second co-primary outcome: composite of resuscitated cardiac arrest, heart failure, and revascularization
Baseline Characteristics Group A (n= 3,180) Group B (n= 3,181) Group C (n= 3,176) Group D (n= 3,168)
Age (years) 65.7 65.8 65.6 65.7
Female (%) 46.1 46.7 45.5 46.7
Systolic (mmHg) 138.2 137.9 138.2 137.9
Diastolic (mmHg) 81.9 81.8 82.0 81.8
Heart rate (beats/min) 73.0 72.6 72.9 72.5
Total cholesterol (mg/dl) 201.3 201.8 201.5 201.2
Low-density lipoprotein (mg/dL) 127.0 128.6 127.9 127.9
High-density lipoprotein (mg/dL) 44.7 44.8 45.1 44.8
Triglycerides (mg/dL) 128.3 129.2 126.5 126.5
Chinese (%) 29.0 29.3 29.0 28.9
Hispanic (%) 27.2 27.7 27.6 27.7
White (%) 20.5 20.0 19.9 19.8
South Asian (%) 14.6 14.5 14.7 14.5
Other Asian (%) 5.3 5.4 5.4 5.7
Black (%) 1.8 1.7 1.8 1.7
Other ethnic group (%) 1.6 1.4 1.5 1.7
Results Group A (n= 3,180) Group B (n= 3,181) Group C (n= 3,176) Group D (n= 3,168) Hazard ratio group A vs. group D (95% CI) p value
First co-primary outcome (%) 3.6 3.8 4.6 5.0 0.71 (0.56-0.90) 0.005
Second co-primary outcome (%) 4.3 4.4 5.5 5.9 0.72 (0.57-0.89) 0.003
Adverse Events Common Adverse Events: N/A
Serious Adverse Events: N/A
Percentage that Discontinued due to Adverse Events: N/A
Study Author Conclusions In the HOPE-3 trial, treatment with fixed doses of rosuvastatin and two antihypertensive agents was associated with a significantly lower risk of cardiovascular events than the risk with placebo among intermediate-risk persons without previous cardiovascular disease.

 

This study supports the theory that lowering both lipid and blood-pressure in intermediate-risk patients reduces the risk of cardiovascular events significantly in various ethnic groups. One of the limitations is that the first co-primary outcome is death from cardiovascular events; however, the inclusion criteria was patients with intermediate risk. Therefore, the result of the first co-primary outcome might not reflect the benefit of the combination therapy in only five years. There are guidelines for high blood pressure and high cholesterol individually but no guideline for controlling both blood pressure and cholesterol to prevent cardiovascular events. More studies are needed with either higher doses or more high risk patients.

 

References

  1. James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the management of high blood pressure in adults. Report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA 2013 Dec 18. doi: 10.1001/jama.2013.284427.
  2. Weber MA, Schiffrin EL, White WB, et al. Clinical practice guidelines for the management of hypertension in the community: a statement by the American Society of Hypertension and the International Society of Hypertension. J Clin Hypertens (Greenwich). 2014;16(1):14-26.
  3. Stone NJ, Robinson JG, Lichtenstein AH, et al. 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines.J Am Coll Cardiol. 2014;63(25_PA):2889-2934. doi: 10.1016/j.jacc.2013.11.002.
  4. Yusuf S. Two decades of progress in preventing vascular disease. Lancet. 2002;360(9326):2-3.
  5. Yusuf S, Lonn E, Pais P, et al. Blood-Pressure and Cholesterol Lowering in Persons without Cardiovascular Disease. N Engl J Med. 2016;374(21):2032-43.

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