Hypertension Drives Up Risks from Oral Contraceptives

MIAMI BEACH – Results of a comprehensive study looking at almost 1.6 million women suggest a small but real elevated risk of thrombotic stroke and myocardial infarction associated with use of hormonal contraception among women who have hypertension.

Even hypertensive women who do not smoke were at increased risk, which suggests that there needs to be a shift in how physicians counsel women regarding use of oral contraception, according to Dr. Keith C. Ferdinand, professor of clinical medicine at Tulane University, New Orleans, and a cardiologist at the Tulane Heart and Vascular Institute in that city.

"Clearly this does suggest that if a patient is on oral contraceptives, you cannot tell them they won’t have a stroke or MI just because they don’t smoke," Dr. Ferdinand said at the meeting, which was sponsored by the International Society on Hypertension in Blacks.

"I was a little surprised by the Danish study," Dr. Ferdinand said (N. Engl. J. Med. 2012;366:2257-66). "The rule of thumb is – if you look at the package insert and at what most clinicians believe – if you’re not over 35 and you don’t smoke, you’re [essentially] okay. That is what we tell patients."

"The Danish registry suggests that although the attributable risk was low (41.5 cases out of 10,000 person-years), it’s really there."

World Health Organization guidelines state that OCs are absolutely contraindicated in women with blood pressure greater than 160 mm Hg/100 mm Hg. "You may say to the patient that if their blood pressure is significantly elevated, they may need another form of contraception." Dr. Ferdinand urged additional caution because even milder blood pressure elevations could be associated with increased risks. The good news, he added, is that the increased risk for MI and stroke does reverse with cessation of OC use.

In the Danish study, researchers assessed 1,626,158 nonpregnant women with no previous cardiovascular disease. This represented essentially the entire Danish female population aged 15-49 years, Dr. Ferdinand said. A total 3,311 thrombotic strokes and 1,725 first MIs occurred out of more than 14 million total person-years of observation in this historical cohort study.

Relative risks increased with hormonal contraceptive use. "Using contraceptive pills with estrogen and progestin did indeed increase the risk of stroke and MI," Dr. Ferdinand said, but the variation by dosage was modest. For example, higher doses of estrogen did appear to increase the relative risk of stroke, but dosing of progestin had little effect, he added.

Specifically, the absolute risks for MI and stroke were increased by a factor of 0.9 to 1.7 with oral contraceptives that included ethinyl estradiol at a dose of 20 mcg, and by a factor of 1.3 to 2.3 with OCs that included ethinyl estradiol at a dose of 30-40 mcg.

Another finding was that if a woman had diabetes, her relative risk of thrombotic stroke was 2.73 and her relative risk for an MI was 4.66. If a woman had hypertension, there was almost an equivalent increased risk of stroke (RR, 2.3), Dr. Ferdinand said. The relative risk of MI associated with hypertension was 2.17.

Dr. Ferdinand is a consultant to Astra Zeneca, Daiichi Sankyo, Forest, and Novartis. He is on the speakers bureau for Astra Zeneca, Forest, Takeda, and Novartis. He also receives grant research support from Eli Lilly, Daiichi Sankyo, Forest, and Novartis.

MIAMI BEACH – Results of a comprehensive study looking at almost 1.6 million women suggest a small but real elevated risk of thrombotic stroke and myocardial infarction associated with use of hormonal contraception among women who have hypertension.

Even hypertensive women who do not smoke were at increased risk, which suggests that there needs to be a shift in how physicians counsel women regarding use of oral contraception, according to Dr. Keith C. Ferdinand, professor of clinical medicine at Tulane University, New Orleans, and a cardiologist at the Tulane Heart and Vascular Institute in that city.

"Clearly this does suggest that if a patient is on oral contraceptives, you cannot tell them they won’t have a stroke or MI just because they don’t smoke," Dr. Ferdinand said at the meeting, which was sponsored by the International Society on Hypertension in Blacks.

"I was a little surprised by the Danish study," Dr. Ferdinand said (N. Engl. J. Med. 2012;366:2257-66). "The rule of thumb is – if you look at the package insert and at what most clinicians believe – if you’re not over 35 and you don’t smoke, you’re [essentially] okay. That is what we tell patients."

"The Danish registry suggests that although the attributable risk was low (41.5 cases out of 10,000 person-years), it’s really there."

World Health Organization guidelines state that OCs are absolutely contraindicated in women with blood pressure greater than 160 mm Hg/100 mm Hg. "You may say to the patient that if their blood pressure is significantly elevated, they may need another form of contraception." Dr. Ferdinand urged additional caution because even milder blood pressure elevations could be associated with increased risks. The good news, he added, is that the increased risk for MI and stroke does reverse with cessation of OC use.

In the Danish study, researchers assessed 1,626,158 nonpregnant women with no previous cardiovascular disease. This represented essentially the entire Danish female population aged 15-49 years, Dr. Ferdinand said. A total 3,311 thrombotic strokes and 1,725 first MIs occurred out of more than 14 million total person-years of observation in this historical cohort study.

Relative risks increased with hormonal contraceptive use. "Using contraceptive pills with estrogen and progestin did indeed increase the risk of stroke and MI," Dr. Ferdinand said, but the variation by dosage was modest. For example, higher doses of estrogen did appear to increase the relative risk of stroke, but dosing of progestin had little effect, he added.

Specifically, the absolute risks for MI and stroke were increased by a factor of 0.9 to 1.7 with oral contraceptives that included ethinyl estradiol at a dose of 20 mcg, and by a factor of 1.3 to 2.3 with OCs that included ethinyl estradiol at a dose of 30-40 mcg.

Another finding was that if a woman had diabetes, her relative risk of thrombotic stroke was 2.73 and her relative risk for an MI was 4.66. If a woman had hypertension, there was almost an equivalent increased risk of stroke (RR, 2.3), Dr. Ferdinand said. The relative risk of MI associated with hypertension was 2.17.

Dr. Ferdinand is a consultant to Astra Zeneca, Daiichi Sankyo, Forest, and Novartis. He is on the speakers bureau for Astra Zeneca, Forest, Takeda, and Novartis. He also receives grant research support from Eli Lilly, Daiichi Sankyo, Forest, and Novartis.

MIAMI BEACH – Results of a comprehensive study looking at almost 1.6 million women suggest a small but real elevated risk of thrombotic stroke and myocardial infarction associated with use of hormonal contraception among women who have hypertension.

Even hypertensive women who do not smoke were at increased risk, which suggests that there needs to be a shift in how physicians counsel women regarding use of oral contraception, according to Dr. Keith C. Ferdinand, professor of clinical medicine at Tulane University, New Orleans, and a cardiologist at the Tulane Heart and Vascular Institute in that city.

"Clearly this does suggest that if a patient is on oral contraceptives, you cannot tell them they won’t have a stroke or MI just because they don’t smoke," Dr. Ferdinand said at the meeting, which was sponsored by the International Society on Hypertension in Blacks.

"I was a little surprised by the Danish study," Dr. Ferdinand said (N. Engl. J. Med. 2012;366:2257-66). "The rule of thumb is – if you look at the package insert and at what most clinicians believe – if you’re not over 35 and you don’t smoke, you’re [essentially] okay. That is what we tell patients."

"The Danish registry suggests that although the attributable risk was low (41.5 cases out of 10,000 person-years), it’s really there."

World Health Organization guidelines state that OCs are absolutely contraindicated in women with blood pressure greater than 160 mm Hg/100 mm Hg. "You may say to the patient that if their blood pressure is significantly elevated, they may need another form of contraception." Dr. Ferdinand urged additional caution because even milder blood pressure elevations could be associated with increased risks. The good news, he added, is that the increased risk for MI and stroke does reverse with cessation of OC use.

In the Danish study, researchers assessed 1,626,158 nonpregnant women with no previous cardiovascular disease. This represented essentially the entire Danish female population aged 15-49 years, Dr. Ferdinand said. A total 3,311 thrombotic strokes and 1,725 first MIs occurred out of more than 14 million total person-years of observation in this historical cohort study.

Relative risks increased with hormonal contraceptive use. "Using contraceptive pills with estrogen and progestin did indeed increase the risk of stroke and MI," Dr. Ferdinand said, but the variation by dosage was modest. For example, higher doses of estrogen did appear to increase the relative risk of stroke, but dosing of progestin had little effect, he added.

Specifically, the absolute risks for MI and stroke were increased by a factor of 0.9 to 1.7 with oral contraceptives that included ethinyl estradiol at a dose of 20 mcg, and by a factor of 1.3 to 2.3 with OCs that included ethinyl estradiol at a dose of 30-40 mcg.

Another finding was that if a woman had diabetes, her relative risk of thrombotic stroke was 2.73 and her relative risk for an MI was 4.66. If a woman had hypertension, there was almost an equivalent increased risk of stroke (RR, 2.3), Dr. Ferdinand said. The relative risk of MI associated with hypertension was 2.17.

Dr. Ferdinand is a consultant to Astra Zeneca, Daiichi Sankyo, Forest, and Novartis. He is on the speakers bureau for Astra Zeneca, Forest, Takeda, and Novartis. He also receives grant research support from Eli Lilly, Daiichi Sankyo, Forest, and Novartis.