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  Table of Contents  
LETTER TO THE EDITOR
Year : 2017  |  Volume : 8  |  Issue : 1  |  Page : 49-50  

The 'HOPE' for primary prevention of cardiovascular disease: An Asian perspective


Department of Pharmacology, Kasturba Medical College, Manipal University, Mangaluru, Karnataka, India

Date of Web Publication21-Apr-2017

Correspondence Address:
Ashwin Kamath
Department of Pharmacology, Kasturba Medical College, Manipal University, Mangalore, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0976-9234.204917

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How to cite this article:
Pai SB, Kamath A. The 'HOPE' for primary prevention of cardiovascular disease: An Asian perspective. J Pharm Negative Results 2017;8:49-50

How to cite this URL:
Pai SB, Kamath A. The 'HOPE' for primary prevention of cardiovascular disease: An Asian perspective. J Pharm Negative Results [serial online] 2017 [cited 2017 Sep 23];8:49-50. Available from: http://www.pnrjournal.com/text.asp?2017/8/1/49/204917

Dear Sir,

Cardiovascular diseases (CVDs) are a leading cause of morbidity and mortality. Hence, effective pharmacological primary prevention strategies are of considerable interest. Clinical studies of primary prevention strategies have shown evidence of decline in cardiovascular mortality in the western population.[1] However, the Asian population has not been represented well in previous Blood Pressure (BP) and cholesterol lowering trials in primary prevention. In view of this, the results of the recently reported Heart Outcome Prevention Evaluation-3 (HOPE-3) trial, a large multicenter international trial with over half the subjects enrolled from Asian countries, is of particular interest from the Asian perspective.[2],[3] The study is also important because it adopted a broad population-based treatment strategy wherein, men (≥55 years) and women (≥ 65 years) without CVD and with at least one additional risk factor besides age were included. A similar age-based, mass treatment strategy was proposed earlier for the polypill, a fixed dose combination of aspirin, statin, and two or three antihypertensive drugs.[4] The polypill was found to be effective in secondary prevention of CVD. The combination of multiple drugs for CVD in a single formulation ensured better compliance and intake of all the key medications.[5] However, the usefulness of polypill as a primary preventive measure has not been proven despite the initial enthusiasm regarding its effectiveness.[4] The HOPE-3 trial attempted to study the efficacy of a combination of statin with antihypertensive (rosuvastatin + candesartan with hydrochlorothiazide) in a primary prevention setting. The study found that BP and cholesterol lowering with the drug combination resulted in lower risk of cardiovascular events compared to placebo among persons with intermediate risk without evidence of CVD.[3] The study also reported the subgroup analysis for the primary (composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke) and secondary outcomes (primary outcome plus heart failure, cardiac arrest, or revascularization) based on ethnicity in a supplementary appendix. The data provided shows that the hazard ratio for the study outcomes in the Asian population almost equals one [primary outcome: 0.95 (0.58-1.55); secondary outcome: 0.93 (0.58-1.48)]. This is in contrast to results in the European population [primary outcome: 0.51 (0.28-0.93); secondary outcome: 0.46 (0.27-0.79)].[5] The data further shows that the reduced benefit in Asian population was due to the antihypertensive combination which nullified the benefits of rosuvastatin.[5] When the entire study population was taken into account, the drug combination produced the maximum benefit in those with higher blood pressure (upper one third of the blood pressure range of the study sample) while in the rest, statin alone provided the maximum benefit. Although these data (for ethnicity) are from subgroup analysis, there are sufficient grounds to be cautious in adopting such a primary prevention strategy in the Asian population without further studies. Ignoring the possible ethnic differences in face of positive results from trials involving a large western population may not provide the anticipated benefits in the Asian population. In fact, there is a large scope for addressing the modifiable risk factors for CVD by non-pharmacological intervention. Abnormal lipids, smoking, hypertension, diabetes, abdominal obesity, psychosocial factors, consumption of fruits and vegetables, alcohol intake, and physical activity have been shown to account for 90% of the population attributable risk for acute myocardial infarction.[6] In the absence of a well-established pharmacological strategy, interventions to modify diet and lifestyle etc., are the hope for a healthier society.[7] Such interventions would have an impact well beyond the decrease in the cardiovascular events.

To conclude, although the HOPE trial showed an overall beneficial effect of combination of statin and antihypertensive in decreasing CVD outcomes in patients at low risk of CVD, the data specific to the Asian population shows that the combination did not provide the anticipated benefit unlike in the western population. Hence, the study outcome is negative from an Asian perspective which needs to be taken into consideration while designing pharmacological preventive measures for cardiovascular disease in the Asian population.

Financial support and sponsorship

Nil

Conflicts of interest

There are no conflicts of interest



 
   References Top

1.
Prabhakaran D, Jeemon P, Roy A. Cardiovascular Diseases in India. Circulation 2016;133:1605-20.  Back to cited text no. 1
    
2.
Waters DD, KH-Y Chau. Tribulations of recent Cardiology trials, the audacity of Hope, and HOPE-3. Can J Cardiol 2016;32:275-7.  Back to cited text no. 2
    
3.
Yusuf S, Lonn E, Pais P, Bosch J, López-Jaramillo P, Zhu J. Blood-Pressure and Cholesterol lowering in persons without Cardiovascular Disease. N Engl J Med 2016;374:2032-43.  Back to cited text no. 3
    
4.
Huffman MD, The Polypill: From promise to pragmatism. PLoS Med 2015;12:e1001862.  Back to cited text no. 4
    
5.
Yusuf S, Lonn E, Pais P, Bosch J, López-Jaramillo P, Zhu J. Blood-Pressure and Cholesterol Lowering in Persons without Cardiovascular Disease.[Supplementary appendix] [Internet]. N. Engl. J. Med 2016;Available from: http://www.nejm.org/doi/suppl/10.1056/NEJMoa1600177/suppl_file/nejmoa1600177_appendix.pdf. [Last accessed on 2016 Aug 1]  Back to cited text no. 5
    
6.
Yusuf S, Hawken S, Ounpuu S, Dans T, Avezum A, Lanas F. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): Case-control study. Lancet. 2004;364:937-52.  Back to cited text no. 6
    
7.
Sallis JF, Cerin E, Conway TL, Adams MA, Frank LD, Pratt M. Physical activity in relation to urban environments in 14 cities worldwide: A cross-sectional study. Lancet. 2016;387:2207-17.  Back to cited text no. 7
    




 

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